rs4129566

chr4-173626006-T-C

Variant summary

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

The ENST00000647106.1(HAND2-AS1):n.142-8605T>C 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 0.113 in 152,264 control chromosomes in the GnomAD database, including 1,027 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 0.11 (1027 hom., cov: 32)
• Consequence: HAND2-AS1 ENST00000647106.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.106

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAND2-AS1	ENST00000647106.1	n.142-8605T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17165 AN: 152146 Hom.: 1026 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.0822

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.00673

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.113 AC: 17175 AN: 152264 Hom.: 1027 Cov.: 32 AF XY: 0.109 AC XY: 8116 AN XY: 74432

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.0821

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.00674

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.112

Alfa AF: 0.121 Hom.: 126

Bravo AF: 0.110

Asia WGS AF: 0.0680 AC: 237 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	7.3
Dann	Benign	0.89

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4129566; hg19: chr4-174547157;