rs4129566

Variant names:

• chr4-173626006-T-C
• rs4129566
• ENST00000647106.1:n.142-8605T>C

Variant summary

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

The ENST00000647106.1(HAND2-AS1):​n.142-8605T>C variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.106
• Publications: 3 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=-0.8).
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAND2-AS1	ENST00000647106.1	n.142-8605T>C		intron_variant	Intron 1 of 2
HAND2-AS1	ENST00000829139.1	n.226+16795T>C		intron_variant	Intron 1 of 2
HAND2-AS1	ENST00000829140.1	n.388-8605T>C		intron_variant	Intron 1 of 1

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

African (AFR) AF: 0.102 AC: 4259 AN: 41556

American (AMR) AF: 0.0821 AC: 1256 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 459 AN: 3470

East Asian (EAS) AF: 0.00674 AC: 35 AN: 5192

South Asian (SAS) AF: 0.122 AC: 590 AN: 4820

European-Finnish (FIN) AF: 0.109 AC: 1152 AN: 10608

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9040 AN: 68008

Other (OTH) AF: 0.112 AC: 237 AN: 2108

Alfa AF: 0.121 Hom.: 132

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
PhyloP100		0.11

Splicing

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

Other links and lift over

dbSNP: rs4129566; hg19: chr4-174547157;