X-8533079-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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 (★).

• 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.186

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: 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_single_submitter, 1 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	c.1985-26G>T		intron_variant		ENST00000262648.8

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.304 AC: 33808 AN: 111112 Hom.: 3873 Cov.: 23 AF XY: 0.296 AC XY: 9854 AN XY: 33344

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

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.: 15 AF XY: 0.313 AC XY: 73498 AN XY: 234725

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.: 23 AF XY: 0.295 AC XY: 9871 AN XY: 33406

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

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

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

Other links and lift over

dbSNP: rs41303179; hg19: chrX-8501120; COSMIC: COSV52924123; COSMIC: COSV52924123;