NM_000216.4:c.1833C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_000216.4(ANOS1):c.1833C>T(p.Ile611Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 12116 hom., 17436 hem., cov: 23)

Exomes 𝑓: 0.62 ( 147868 hom. 220049 hem. )

Failed GnomAD Quality Control

Consequence

ANOS1
NM_000216.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.356

Publications

14 publications found

Variant links:

Genes affected

ANOS1 (HGNC:6211): (anosmin 1) Mutations in this gene cause the X-linked Kallmann syndrome. The encoded protein is similar in sequence to proteins known to function in neural cell adhesion and axonal migration. In addition, this cell surface protein is N-glycosylated and may have anti-protease activity. [provided by RefSeq, Jul 2008]

ANOS1 Gene-Disease associations (from GenCC):

hypogonadotropic hypogonadism 1 with or without anosmia
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
Kallmann syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ANOS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant X-8535600-G-A is Benign according to our data. Variant chrX-8535600-G-A is described in ClinVar as Benign. ClinVar VariationId is 255564.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.356 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANOS1	NM_000216.4 link	c.1833C>T	p.Ile611Ile	synonymous_variant	Exon 12 of 14	ENST00000262648.8	NP_000207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANOS1	ENST00000262648.8 link	c.1833C>T	p.Ile611Ile	synonymous_variant	Exon 12 of 14	1	NM_000216.4	ENSP00000262648.3
ANOS1	ENST00000481896.1 link	n.378C>T		non_coding_transcript_exon_variant	Exon 2 of 2	4

Frequencies

GnomAD3 genomes

AF:

0.535

AC:

59407

AN:

110963

Hom.:

12123

Cov.:

show subpopulations

Gnomad AFR

AF:

0.332

Gnomad AMI

AF:

0.543

Gnomad AMR

AF:

0.470

Gnomad ASJ

AF:

0.630

Gnomad EAS

AF:

0.654

Gnomad SAS

AF:

0.379

Gnomad FIN

AF:

0.585

Gnomad MID

AF:

0.610

Gnomad NFE

AF:

0.655

Gnomad OTH

AF:

0.555

GnomAD2 exomes

AF:

0.555

AC:

100457

AN:

180887

AF XY:

0.559

show subpopulations

Gnomad AFR exome

AF:

0.333

Gnomad AMR exome

AF:

0.357

Gnomad ASJ exome

AF:

0.657

Gnomad EAS exome

AF:

0.655

Gnomad FIN exome

AF:

0.594

Gnomad NFE exome

AF:

0.658

Gnomad OTH exome

AF:

0.594

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.624

AC:

680341

AN:

1090675

Hom.:

147868

Cov.:

AF XY:

0.616

AC XY:

220049

AN XY:

357275

show subpopulations

African (AFR)

AF:

0.323

AC:

8498

AN:

26280

American (AMR)

AF:

0.371

AC:

13006

AN:

35050

Ashkenazi Jewish (ASJ)

AF:

0.652

AC:

12607

AN:

19346

East Asian (EAS)

AF:

0.665

AC:

20055

AN:

30163

South Asian (SAS)

AF:

0.407

AC:

21949

AN:

53938

European-Finnish (FIN)

AF:

0.588

AC:

23811

AN:

40478

Middle Eastern (MID)

AF:

0.561

AC:

2310

AN:

4120

European-Non Finnish (NFE)

AF:

0.659

AC:

550261

AN:

835434

Other (OTH)

AF:

0.607

AC:

27844

AN:

45866

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

8329

16657

24986

33314

41643

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16304

32608

48912

65216

81520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.535

AC:

59394

AN:

111017

Hom.:

12116

Cov.:

AF XY:

0.524

AC XY:

17436

AN XY:

33289

show subpopulations

African (AFR)

AF:

0.331

AC:

10136

AN:

30583

American (AMR)

AF:

0.470

AC:

4954

AN:

10541

Ashkenazi Jewish (ASJ)

AF:

0.630

AC:

1654

AN:

2626

East Asian (EAS)

AF:

0.653

AC:

2267

AN:

3472

South Asian (SAS)

AF:

0.377

AC:

991

AN:

2630

European-Finnish (FIN)

AF:

0.585

AC:

3452

AN:

5901

Middle Eastern (MID)

AF:

0.623

AC:

134

AN:

215

European-Non Finnish (NFE)

AF:

0.654

AC:

34591

AN:

52854

Other (OTH)

AF:

0.558

AC:

848

AN:

1519

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

966

1931

2897

3862

4828

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

536

1072

1608

2144

2680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.529

Hom.:

13247

Bravo

AF:

0.523

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Jul 27, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Hypogonadotropic hypogonadism 1 with or without anosmia

Benign:2

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.20

(source)

DANN

Benign

0.66

PhyloP100

-0.36

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over