chrX-8534047-G-A

Variant names:

• chrX-8534047-G-A
• rs56051736
• NM_000216.4:c.1984+272C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000216.4(ANOS1):​c.1984+272C>T variant causes a intron 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 0.078 (431 hom., 2351 hem., cov: 20)
• Consequence: ANOS1 NM_000216.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.451
• Publications: 0 publications found

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: Labcorp Genetics (formerly Invitae), ClinGen
• Kallmann syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant X-8534047-G-A is Benign according to our data. Variant chrX-8534047-G-A is described in ClinVar as Benign. ClinVar VariationId is 1273399.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000216.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANOS1	NM_000216.4	MANE Select	c.1984+272C>T		intron	N/A	NP_000207.2	P23352

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANOS1	ENST00000262648.8	TSL:1 MANE Select	c.1984+272C>T		intron	N/A	ENSP00000262648.3	P23352
	ANOS1	ENST00000921740.1		c.1981+272C>T		intron	N/A	ENSP00000591799.1
	ANOS1	ENST00000921741.1		c.1837+272C>T		intron	N/A	ENSP00000591800.1

Frequencies

GnomAD3 genomes AF: 0.0778 AC: 8380 AN: 107662 Hom.: 428 Cov.: 20

Gnomad AFR AF: 0.0209

Gnomad AMI AF: 0.0975

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.0668

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0819

Gnomad NFE AF: 0.0671

Gnomad OTH AF: 0.0919

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0779 AC: 8392 AN: 107688 Hom.: 431 Cov.: 20 AF XY: 0.0776 AC XY: 2351 AN XY: 30304

African (AFR) AF: 0.0209 AC: 622 AN: 29767

American (AMR) AF: 0.242 AC: 2383 AN: 9838

Ashkenazi Jewish (ASJ) AF: 0.0668 AC: 174 AN: 2604

East Asian (EAS) AF: 0.177 AC: 599 AN: 3379

South Asian (SAS) AF: 0.117 AC: 276 AN: 2362

European-Finnish (FIN) AF: 0.118 AC: 621 AN: 5255

Middle Eastern (MID) AF: 0.0861 AC: 18 AN: 209

European-Non Finnish (NFE) AF: 0.0671 AC: 3498 AN: 52133

Other (OTH) AF: 0.0922 AC: 135 AN: 1464

Alfa AF: 0.0770 Hom.: 429

Bravo AF: 0.0923

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.72
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs56051736; hg19: chrX-8502088;