chr4-173633681-A-G

Position:

• chr4-173633681-A-G

Variant summary

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

The ENST00000647106.1(HAND2-AS1):​n.142-930A>G 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 0.117 in 787,432 control chromosomes in the GnomAD database, including 6,122 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 (1042 hom., cov: 32)
  • Exomes 𝑓: 0.12 (5080 hom.)
• Consequence: HAND2-AS1 ENST00000647106.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85

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]

RANP6 (HGNC:39861): (RAN pseudogene 6)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HAND2-AS1	ENST00000647106.1	n.142-930A>G		intron_variant, non_coding_transcript_variant
RANP6	ENST00000413691.2			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17243 AN: 152086 Hom.: 1041 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.0823

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.00675

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.113

GnomAD4 exome AF: 0.118 AC: 75108 AN: 635228 Hom.: 5080 Cov.: 8 AF XY: 0.119 AC XY: 40536 AN XY: 339322

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.0650

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.00565

Gnomad4 SAS exome AF: 0.132

Gnomad4 FIN exome AF: 0.107

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.119

GnomAD4 genome AF: 0.113 AC: 17253 AN: 152204 Hom.: 1042 Cov.: 32 AF XY: 0.109 AC XY: 8148 AN XY: 74412

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.0822

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.00676

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.113

Alfa AF: 0.122 Hom.: 130

Bravo AF: 0.111

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	-0.58
CADD	Benign	7.2
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11944332; hg19: chr4-174554832; COSMIC: COSV69607648;