X-8553929-ATAAG-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000216.4(ANOS1):c.1354+19_1354+22delCTTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00748 in 1,187,970 control chromosomes in the GnomAD database, including 411 homozygotes. There are 2,314 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 208 hom., 1137 hem., cov: 21)

Exomes 𝑓: 0.0043 ( 203 hom. 1177 hem. )

Consequence

ANOS1
NM_000216.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0330

Publications

0 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 -16 ACMG points.

BP6

Variant X-8553929-ATAAG-A is Benign according to our data. Variant chrX-8553929-ATAAG-A is described in CliVar as Benign. Clinvar id is 516595.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-8553929-ATAAG-A is described in CliVar as Benign. Clinvar id is 516595.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-8553929-ATAAG-A is described in CliVar as Benign. Clinvar id is 516595.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-8553929-ATAAG-A is described in CliVar as Benign. Clinvar id is 516595.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-8553929-ATAAG-A is described in CliVar as Benign. Clinvar id is 516595.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANOS1	NM_000216.4 link	c.1354+19_1354+22delCTTA		intron_variant	Intron 9 of 13	ENST00000262648.8	NP_000207.2	P23352

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANOS1	ENST00000262648.8 link	c.1354+19_1354+22delCTTA		intron_variant	Intron 9 of 13	1	NM_000216.4	ENSP00000262648.3		P23352

Frequencies

GnomAD3 genomes

AF:

0.0380

AC:

4255

AN:

111959

Hom.:

207

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00889

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000744

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0126

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.0271

GnomAD2 exomes

AF:

0.0106

AC:

1932

AN:

182742

AF XY:

0.00688

show subpopulations

Gnomad AFR exome

AF:

0.133

Gnomad AMR exome

AF:

0.00478

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000368

Gnomad OTH exome

AF:

0.00421

GnomAD4 exome

AF:

0.00428

AC:

4610

AN:

1075962

Hom.:

203

AF XY:

0.00342

AC XY:

1177

AN XY:

343952

show subpopulations

African (AFR)

AF:

0.142

AC:

3673

AN:

25932

American (AMR)

AF:

0.00631

AC:

222

AN:

35171

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19243

East Asian (EAS)

AF:

0.0000332

AC:

AN:

30116

South Asian (SAS)

AF:

0.000429

AC:

AN:

53644

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40487

Middle Eastern (MID)

AF:

0.0123

AC:

AN:

4077

European-Non Finnish (NFE)

AF:

0.000190

AC:

156

AN:

821917

Other (OTH)

AF:

0.0107

AC:

485

AN:

45375

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

150

300

449

599

749

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

220

330

440

550

<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

AF:

0.0382

AC:

4278

AN:

112008

Hom.:

208

Cov.:

AF XY:

0.0332

AC XY:

1137

AN XY:

34208

show subpopulations

African (AFR)

AF:

0.134

AC:

4121

AN:

30677

American (AMR)

AF:

0.00888

AC:

AN:

10590

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2651

East Asian (EAS)

AF:

0.00

AC:

AN:

3570

South Asian (SAS)

AF:

0.000747

AC:

AN:

2678

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6113

Middle Eastern (MID)

AF:

0.00917

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.000338

AC:

AN:

53291

Other (OTH)

AF:

0.0268

AC:

AN:

1532

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

135

270

406

541

676

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<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:

0.0203

Hom.:

111

Bravo

AF:

0.0446

Asia WGS

AF:

0.0110

AC:

AN:

2522

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 13, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Hypogonadotropic hypogonadism 1 with or without anosmia

Benign:1

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Mar 02, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.033

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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