3-186620636-A-G

Variant names:

• chr3-186620636-A-G
• rs1071592
• NM_001622.4:c.810A>G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001622.4(AHSG):​c.810A>G​(p.Thr270Thr) variant causes a synonymous 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. 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 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.399

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:55915): (HRG and FETUB antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-0.399 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHSG	NM_001622.4	c.810A>G	p.Thr270Thr	synonymous_variant	Exon 7 of 7	ENST00000411641.7	NP_001613.2
AHSG	NM_001354571.2	c.813A>G	p.Thr271Thr	synonymous_variant	Exon 7 of 7		NP_001341500.1
AHSG	NM_001354572.2	c.807A>G	p.Thr269Thr	synonymous_variant	Exon 7 of 7		NP_001341501.1
AHSG	NM_001354573.2	c.726A>G	p.Thr242Thr	synonymous_variant	Exon 6 of 6		NP_001341502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHSG	ENST00000411641.7	c.810A>G	p.Thr270Thr	synonymous_variant	Exon 7 of 7	1	NM_001622.4	ENSP00000393887.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 66

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.0
DANN	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1071592; hg19: chr3-186338425;