Variant 3-186617180-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001622.4(AHSG):c.410-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000541 in 1,605,738 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00048 ( 5 hom. )

Consequence

AHSG
NM_001622.4 splice_region, intron

Scores

Splicing: ADA: 0.00002577

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.425

Variant links:

Genes affected

AHSG (HGNC:349): (alpha 2-HS glycoprotein) The protein encoded by this gene is a negatively-charged serum glycoprotein that is synthesized by hepatocytes. The encoded protein consists of two polypeptide chains, which are both cleaved from a proprotein encoded from a single mRNA. It is involved in several processes, including endocytosis, brain development, and the formation of bone tissue. Defects in this gene are a cause of susceptibility to leanness. [provided by RefSeq, Aug 2017]

AHSG links:

AHSG (HGNC:):

AHSG links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 3-186617180-C-T is Benign according to our data. Variant chr3-186617180-C-T is described in ClinVar as [Benign]. Clinvar id is 737830.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
AHSG	NM_001622.4 linkuse as main transcript	c.410-7C>T	splice_region_variant, intron_variant	ENST00000411641.7	NP_001613.2	P02765
AHSG	NM_001354571.2 linkuse as main transcript	c.410-4C>T	splice_region_variant, intron_variant		NP_001341500.1
AHSG	NM_001354572.2 linkuse as main transcript	c.407-7C>T	splice_region_variant, intron_variant		NP_001341501.1
AHSG	NM_001354573.2 linkuse as main transcript	c.410-7C>T	splice_region_variant, intron_variant		NP_001341502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHSG	ENST00000411641.7 linkuse as main transcript	c.410-7C>T		splice_region_variant, intron_variant		1	NM_001622.4	ENSP00000393887.2		P02765

Frequencies

GnomAD3 genomes

AF:

0.00110

AC:

167

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0143

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00119

AC:

293

AN:

245668

Hom.:

AF XY:

0.00109

AC XY:

144

AN XY:

132570

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0127

Gnomad NFE exome

AF:

0.000171

Gnomad OTH exome

AF:

0.000667

GnomAD4 exome

AF:

0.000483

AC:

702

AN:

1453422

Hom.:

Cov.:

AF XY:

0.000446

AC XY:

322

AN XY:

722180

show subpopulations

Gnomad4 AFR exome

AF:

0.0000600

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0121

Gnomad4 NFE exome

AF:

0.0000280

Gnomad4 OTH exome

AF:

0.000417

GnomAD4 genome

AF:

0.00110

AC:

167

AN:

152316

Hom.:

Cov.:

AF XY:

0.00172

AC XY:

128

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0143

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000312

Hom.:

Bravo

AF:

0.0000567

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

Labcorp Genetics (formerly Invitae), Labcorp

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.2

DANN

Benign

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000026

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

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