rs1071592

Positions:

• chr3-186620636-A-C
• chr3-186620636-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001622.4(AHSG):​c.810A>C​(p.Thr270=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 1,612,888 control chromosomes in the GnomAD database, including 460,325 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.77 (45925 hom., cov: 31)
  • Exomes 𝑓: 0.75 (414400 hom.)
• Consequence: AHSG NM_001622.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 3-186620636-A-C is Benign according to our data. Variant chr3-186620636-A-C is described in ClinVar as [Benign]. Clinvar id is 1188909.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.399 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AHSG	NM_001622.4	c.810A>C	p.Thr270=	synonymous_variant	7/7	ENST00000411641.7
AHSG	NM_001354571.2	c.813A>C	p.Thr271=	synonymous_variant	7/7
AHSG	NM_001354572.2	c.807A>C	p.Thr269=	synonymous_variant	7/7
AHSG	NM_001354573.2	c.726A>C	p.Thr242=	synonymous_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHSG	ENST00000411641.7	c.810A>C	p.Thr270=	synonymous_variant	7/7	1	NM_001622.4	P3
HRG-AS1	ENST00000630178.2	n.239-40670T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117714 AN: 151914 Hom.: 45887 Cov.: 31

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.836

Gnomad EAS AF: 0.828

Gnomad SAS AF: 0.860

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.801

GnomAD3 exomes AF: 0.758 AC: 190315 AN: 250990 Hom.: 73001 AF XY: 0.767 AC XY: 104000 AN XY: 135610

Gnomad AFR exome AF: 0.852

Gnomad AMR exome AF: 0.628

Gnomad ASJ exome AF: 0.836

Gnomad EAS exome AF: 0.835

Gnomad SAS exome AF: 0.858

Gnomad FIN exome AF: 0.684

Gnomad NFE exome AF: 0.751

Gnomad OTH exome AF: 0.774

GnomAD4 exome AF: 0.751 AC: 1097660 AN: 1460856 Hom.: 414400 Cov.: 66 AF XY: 0.756 AC XY: 548971 AN XY: 726536

Gnomad4 AFR exome AF: 0.849

Gnomad4 AMR exome AF: 0.637

Gnomad4 ASJ exome AF: 0.837

Gnomad4 EAS exome AF: 0.825

Gnomad4 SAS exome AF: 0.855

Gnomad4 FIN exome AF: 0.688

Gnomad4 NFE exome AF: 0.741

Gnomad4 OTH exome AF: 0.777

GnomAD4 genome AF: 0.775 AC: 117807 AN: 152032 Hom.: 45925 Cov.: 31 AF XY: 0.773 AC XY: 57417 AN XY: 74288

Gnomad4 AFR AF: 0.850

Gnomad4 AMR AF: 0.692

Gnomad4 ASJ AF: 0.836

Gnomad4 EAS AF: 0.827

Gnomad4 SAS AF: 0.860

Gnomad4 FIN AF: 0.686

Gnomad4 NFE AF: 0.746

Gnomad4 OTH AF: 0.801

Alfa AF: 0.770 Hom.: 23748

Bravo AF: 0.779

Asia WGS AF: 0.821 AC: 2855 AN: 3478

EpiCase AF: 0.773

EpiControl AF: 0.775

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Alopecia-intellectual disability syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.96
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;