Variant X-8533079-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000216.4(ANOS1):c.1985-26G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 953,021 control chromosomes in the GnomAD database, including 29,369 homozygotes. There are 83,369 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.30 ( 3873 hom., 9871 hem., cov: 23)

Exomes 𝑓: 0.29 ( 25496 hom. 73498 hem. )

Consequence

ANOS1
NM_000216.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.186

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant X-8533079-C-A is Benign according to our data. Variant chrX-8533079-C-A is described in ClinVar as [Benign]. Clinvar id is 1236328.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANOS1	NM_000216.4 linkuse as main transcript	c.1985-26G>T		intron_variant		ENST00000262648.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANOS1	ENST00000262648.8 linkuse as main transcript	c.1985-26G>T		intron_variant		1	NM_000216.4	P1

Frequencies

GnomAD3 genomes

AF:

0.304

AC:

33808

AN:

111112

Hom.:

3873

Cov.:

AF XY:

0.296

AC XY:

9854

AN XY:

33344

show subpopulations

Gnomad AFR

AF:

0.327

Gnomad AMI

AF:

0.326

Gnomad AMR

AF:

0.207

Gnomad ASJ

AF:

0.334

Gnomad EAS

AF:

0.574

Gnomad SAS

AF:

0.289

Gnomad FIN

AF:

0.310

Gnomad MID

AF:

0.289

Gnomad NFE

AF:

0.292

Gnomad OTH

AF:

0.303

GnomAD3 exomes

AF:

0.298

AC:

51473

AN:

172643

Hom.:

5638

AF XY:

0.303

AC XY:

17655

AN XY:

58267

show subpopulations

Gnomad AFR exome

AF:

0.338

Gnomad AMR exome

AF:

0.134

Gnomad ASJ exome

AF:

0.339

Gnomad EAS exome

AF:

0.579

Gnomad SAS exome

AF:

0.315

Gnomad FIN exome

AF:

0.313

Gnomad NFE exome

AF:

0.290

Gnomad OTH exome

AF:

0.290

GnomAD4 exome

AF:

0.289

AC:

243402

AN:

841857

Hom.:

25496

Cov.:

AF XY:

0.313

AC XY:

73498

AN XY:

234725

show subpopulations

Gnomad4 AFR exome

AF:

0.331

Gnomad4 AMR exome

AF:

0.149

Gnomad4 ASJ exome

AF:

0.335

Gnomad4 EAS exome

AF:

0.550

Gnomad4 SAS exome

AF:

0.318

Gnomad4 FIN exome

AF:

0.302

Gnomad4 NFE exome

AF:

0.278

Gnomad4 OTH exome

AF:

0.305

GnomAD4 genome

AF:

0.304

AC:

33824

AN:

111164

Hom.:

3873

Cov.:

AF XY:

0.295

AC XY:

9871

AN XY:

33406

show subpopulations

Gnomad4 AFR

AF:

0.327

Gnomad4 AMR

AF:

0.207

Gnomad4 ASJ

AF:

0.334

Gnomad4 EAS

AF:

0.573

Gnomad4 SAS

AF:

0.289

Gnomad4 FIN

AF:

0.310

Gnomad4 NFE

AF:

0.292

Gnomad4 OTH

AF:

0.306

Alfa

AF:

0.319

Hom.:

3042

Bravo

AF:

0.301

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.70

DANN

Benign

0.44

BranchPoint Hunter

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over