rs12646107

Positions:

• chr4-173594531-A-C

Variant summary

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

The ENST00000647106.1(HAND2-AS1):​n.142-40080A>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 0.112 in 152,286 control chromosomes in the GnomAD database, including 1,084 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 (1084 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: HAND2-AS1 ENST00000647106.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.143 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.142-40080A>C		intron_variant, non_coding_transcript_variant
HAND2-AS1	ENST00000561655.2	n.3831A>C		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes AF: 0.112 AC: 16991 AN: 152168 Hom.: 1080 Cov.: 33

Gnomad AFR AF: 0.0576

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0942

Gnomad ASJ AF: 0.0888

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.115

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.112 AC: 16994 AN: 152286 Hom.: 1084 Cov.: 33 AF XY: 0.112 AC XY: 8335 AN XY: 74462

Gnomad4 AFR AF: 0.0575

Gnomad4 AMR AF: 0.0940

Gnomad4 ASJ AF: 0.0888

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.119

Alfa AF: 0.134 Hom.: 1858

Bravo AF: 0.104

Asia WGS AF: 0.142 AC: 495 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.6
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12646107; hg19: chr4-174515682;