chr3-186620593-G-C

Position:

• chr3-186620593-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001622.4(AHSG):​c.767G>C​(p.Ser256Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 1,592,390 control chromosomes in the GnomAD database, including 349,526 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.66 (33428 hom., cov: 31)
  • Exomes 𝑓: 0.66 (316098 hom.)
• Consequence: AHSG NM_001622.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.591

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]

HRG-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.4840803E-6).
• BP6: Variant 3-186620593-G-C is Benign according to our data. Variant chr3-186620593-G-C is described in ClinVar as [Benign]. Clinvar id is 16044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHSG	NM_001622.4	c.767G>C	p.Ser256Thr	missense_variant	7/7	ENST00000411641.7	NP_001613.2
AHSG	NM_001354571.2	c.770G>C	p.Ser257Thr	missense_variant	7/7		NP_001341500.1
AHSG	NM_001354572.2	c.764G>C	p.Ser255Thr	missense_variant	7/7		NP_001341501.1
AHSG	NM_001354573.2	c.683G>C	p.Ser228Thr	missense_variant	6/6		NP_001341502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHSG	ENST00000411641.7	c.767G>C	p.Ser256Thr	missense_variant	7/7	1	NM_001622.4	ENSP00000393887.2

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100416 AN: 151850 Hom.: 33408 Cov.: 31

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.796

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.654

Gnomad OTH AF: 0.704

GnomAD3 exomes AF: 0.670 AC: 165931 AN: 247658 Hom.: 56374 AF XY: 0.681 AC XY: 91155 AN XY: 133870

Gnomad AFR exome AF: 0.671

Gnomad AMR exome AF: 0.563

Gnomad ASJ exome AF: 0.766

Gnomad EAS exome AF: 0.736

Gnomad SAS exome AF: 0.794

Gnomad FIN exome AF: 0.604

Gnomad NFE exome AF: 0.662

Gnomad OTH exome AF: 0.684

GnomAD4 exome AF: 0.660 AC: 951063 AN: 1440422 Hom.: 316098 Cov.: 44 AF XY: 0.665 AC XY: 473939 AN XY: 712262

Gnomad4 AFR exome AF: 0.671

Gnomad4 AMR exome AF: 0.568

Gnomad4 ASJ exome AF: 0.765

Gnomad4 EAS exome AF: 0.738

Gnomad4 SAS exome AF: 0.788

Gnomad4 FIN exome AF: 0.605

Gnomad4 NFE exome AF: 0.649

Gnomad4 OTH exome AF: 0.682

GnomAD4 genome AF: 0.661 AC: 100482 AN: 151968 Hom.: 33428 Cov.: 31 AF XY: 0.662 AC XY: 49145 AN XY: 74266

Gnomad4 AFR AF: 0.668

Gnomad4 AMR AF: 0.616

Gnomad4 ASJ AF: 0.761

Gnomad4 EAS AF: 0.735

Gnomad4 SAS AF: 0.796

Gnomad4 FIN AF: 0.605

Gnomad4 NFE AF: 0.654

Gnomad4 OTH AF: 0.705

Alfa AF: 0.669 Hom.: 25743

Bravo AF: 0.661

TwinsUK AF: 0.636 AC: 2360

ALSPAC AF: 0.635 AC: 2447

ESP6500AA AF: 0.669 AC: 2946

ESP6500EA AF: 0.652 AC: 5604

ExAC AF: 0.675 AC: 81991

Asia WGS AF: 0.723 AC: 2513 AN: 3478

EpiCase AF: 0.682

EpiControl AF: 0.687

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Alopecia-intellectual disability syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

RECLASSIFIED - AHSG POLYMORPHISM Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Jun 01, 2005

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.22
DANN	Benign	0.48
DEOGEN2	Benign	0.0020	.;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.068	T;T
MetaRNN	Benign	0.0000015	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.63	N;N
REVEL	Benign	0.0050
Sift	Benign	0.93	T;T
Sift4G	Benign	0.54	T;T
Polyphen		0.0	.;B
Vest4		0.033
MPC		0.075
ClinPred		0.00013	T
GERP RS		-3.1
Varity_R		0.034
gMVP		0.16

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

LitVar

Other links and lift over

dbSNP: rs4918; hg19: chr3-186338382; COSMIC: COSV56607208; COSMIC: COSV56607208;