rs4918

Positions:

• chr3-186620593-G-A
• chr3-186620593-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001622.4(AHSG):​c.767G>A​(p.Ser256Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: AHSG NM_001622.4 missense
• Clinical Significance: Not reported in ClinVar
• 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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06969914).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHSG	NM_001622.4	c.767G>A	p.Ser256Asn	missense_variant	7/7	ENST00000411641.7	NP_001613.2
AHSG	NM_001354571.2	c.770G>A	p.Ser257Asn	missense_variant	7/7		NP_001341500.1
AHSG	NM_001354572.2	c.764G>A	p.Ser255Asn	missense_variant	7/7		NP_001341501.1
AHSG	NM_001354573.2	c.683G>A	p.Ser228Asn	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>A	p.Ser256Asn	missense_variant	7/7	1	NM_001622.4	ENSP00000393887.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 44

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.41
DANN	Benign	0.90
DEOGEN2	Benign	0.0097	.;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.24	T;T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.070	T;T
MetaSVM	Benign	-0.96	T
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.67	N;N
REVEL	Benign	0.012
Sift	Benign	0.096	T;T
Sift4G	Benign	0.22	T;T
Polyphen		0.0020	.;B
Vest4		0.086
MutPred		0.26		.;Loss of glycosylation at S257 (P = 0.0289);
MVP		0.18
MPC		0.077
ClinPred		0.088	T
GERP RS		-3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.042
gMVP		0.12

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;