rs4473631

Positions:

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

Variant summary

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

The ENST00000647106.1(HAND2-AS1):​n.141+51779C>A variant causes a intron, non coding transcript 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 ENST00000647106.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
HAND2-AS1	NR_136195.1	n.405-2087C>A		intron_variant, non_coding_transcript_variant
HAND2-AS1	NR_136196.1	n.387-2087C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAND2-AS1	ENST00000647106.1	n.141+51779C>A		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.259

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.802

Gnomad4 EAS AF: 0.645

Gnomad4 SAS AF: 0.738

Gnomad4 FIN AF: 0.705

Gnomad4 NFE AF: 0.740

Gnomad4 OTH AF: 0.621

Alfa AF: 0.692 Hom.: 15724

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4473631; hg19: chr4-174501769;