rs2070633

Positions:

• chr3-186618152-T-C
• chr3-186618152-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001622.4(AHSG):​c.574-384T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 152,030 control chromosomes in the GnomAD database, including 17,920 homozygotes. 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: 𝑓 0.48 (17920 hom., cov: 32)
• Consequence: AHSG NM_001622.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.374

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHSG	NM_001622.4	c.574-384T>C		intron_variant		ENST00000411641.7	NP_001613.2
AHSG	NM_001354571.2	c.577-384T>C		intron_variant			NP_001341500.1
AHSG	NM_001354572.2	c.571-384T>C		intron_variant			NP_001341501.1
AHSG	NM_001354573.2	c.574-384T>C		intron_variant			NP_001341502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHSG	ENST00000411641.7	c.574-384T>C		intron_variant		1	NM_001622.4	ENSP00000393887	P3
HRG-AS1	ENST00000630178.2	n.239-38186A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72538 AN: 151912 Hom.: 17907 Cov.: 32

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.506

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.477 AC: 72583 AN: 152030 Hom.: 17920 Cov.: 32 AF XY: 0.481 AC XY: 35745 AN XY: 74330

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.615

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.521

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.506

Alfa AF: 0.529 Hom.: 42974

Bravo AF: 0.467

Asia WGS AF: 0.558 AC: 1939 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.9
DANN	Benign	0.84

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: rs2070633; hg19: chr3-186335941;