chr17-7113665-A-T

Variant names:

• chr17-7113665-A-T
• rs367953
• NM_001201352.2:c.124+452T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001201352.2(ASGR2):​c.124+452T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 151,242 control chromosomes in the GnomAD database, including 26,710 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 0.59 (26710 hom., cov: 31)
• Consequence: ASGR2 NM_001201352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.120
• Publications: 6 publications found

Genes affected

ASGR2 (HGNC:743): (asialoglycoprotein receptor 2) This gene encodes a subunit of the asialoglycoprotein receptor. This receptor is a transmembrane protein that plays a critical role in serum glycoprotein homeostasis by mediating the endocytosis and lysosomal degradation of glycoproteins with exposed terminal galactose or N-acetylgalactosamine residues. The asialoglycoprotein receptor may facilitate hepatic infection by multiple viruses including hepatitis B, and is also a target for liver-specific drug delivery. The asialoglycoprotein receptor is a hetero-oligomeric protein composed of major and minor subunits, which are encoded by different genes. The protein encoded by this gene is the less abundant minor subunit. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASGR2	NM_001201352.2	c.124+452T>A		intron_variant	Intron 2 of 8	ENST00000691900.1	NP_001188281.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASGR2	ENST00000691900.1	c.124+452T>A		intron_variant	Intron 2 of 8		NM_001201352.2	ENSP00000510808.1

Frequencies

GnomAD3 genomes AF: 0.594 AC: 89740 AN: 151118 Hom.: 26690 Cov.: 31

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.426

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.562

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

GnomAD4 genome AF: 0.594 AC: 89818 AN: 151242 Hom.: 26710 Cov.: 31 AF XY: 0.591 AC XY: 43655 AN XY: 73906

African (AFR) AF: 0.577 AC: 23774 AN: 41198

American (AMR) AF: 0.646 AC: 9825 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 2085 AN: 3450

East Asian (EAS) AF: 0.639 AC: 3263 AN: 5110

South Asian (SAS) AF: 0.519 AC: 2498 AN: 4812

European-Finnish (FIN) AF: 0.524 AC: 5481 AN: 10458

Middle Eastern (MID) AF: 0.435 AC: 127 AN: 292

European-Non Finnish (NFE) AF: 0.606 AC: 40999 AN: 67694

Other (OTH) AF: 0.563 AC: 1179 AN: 2096

Alfa AF: 0.587 Hom.: 3126

Bravo AF: 0.604

Asia WGS AF: 0.587 AC: 2040 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.1
DANN	Benign	0.40
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs367953; hg19: chr17-7016984;