rs4473631

Variant names:

• chr4-173580618-C-A
• rs4473631
• ENST00000503474.5:n.313-2087C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-173580618-C-A
• chr4-173580618-C-T

Variant summary

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

The ENST00000503474.5(HAND2-AS1):​n.313-2087C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 151,802 control chromosomes in the GnomAD database, including 29,266 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 0.58 (29266 hom., cov: 32)
• Consequence: HAND2-AS1 ENST00000503474.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700
• Publications: 1 publications found

Genes affected

HAND2-AS1 (HGNC:48872): (HAND2 antisense RNA 1) Predicted to be involved in positive regulation of gene expression. Predicted to act upstream of or within with a positive effect on cardiac right ventricle morphogenesis. Predicted to act upstream of or within transcription elongation from RNA polymerase II promoter. Predicted to be located in chromatin; cytoplasm; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAND2-AS1	NR_136195.1	n.405-2087C>A		intron_variant	Intron 3 of 4
HAND2-AS1	NR_136196.1	n.387-2087C>A		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAND2-AS1	ENST00000503474.5	n.313-2087C>A		intron_variant	Intron 3 of 4	2
HAND2-AS1	ENST00000504740.5	n.446-2087C>A		intron_variant	Intron 3 of 3	3
HAND2-AS1	ENST00000505817.3	n.300-2087C>A		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88353 AN: 151682 Hom.: 29266 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.961

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.802

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.761

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.582 AC: 88355 AN: 151802 Hom.: 29266 Cov.: 32 AF XY: 0.584 AC XY: 43287 AN XY: 74174

African (AFR) AF: 0.259 AC: 10724 AN: 41366

American (AMR) AF: 0.519 AC: 7906 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.802 AC: 2786 AN: 3472

East Asian (EAS) AF: 0.645 AC: 3326 AN: 5158

South Asian (SAS) AF: 0.738 AC: 3560 AN: 4824

European-Finnish (FIN) AF: 0.705 AC: 7405 AN: 10500

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.740 AC: 50244 AN: 67942

Other (OTH) AF: 0.621 AC: 1308 AN: 2106

Alfa AF: 0.674 Hom.: 63952

Bravo AF: 0.552

Asia WGS AF: 0.610 AC: 2106 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.85
DANN	Benign	0.39
PhyloP100		-0.0070

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4473631; hg19: chr4-174501769;