rs12646107

Variant names:

• chr4-173594531-A-C
• rs12646107
• ENST00000561655.2:n.3831A>C

Variant summary

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

The ENST00000561655.2(HAND2-AS1):​n.3831A>C variant causes a non coding transcript exon 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 ENST00000561655.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150
• Publications: 9 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=-0.9).
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAND2-AS1	ENST00000561655.2	n.3831A>C		non_coding_transcript_exon_variant	Exon 3 of 3	6
HAND2-AS1	ENST00000647106.1	n.142-40080A>C		intron_variant	Intron 1 of 2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0575 AC: 2390 AN: 41568

American (AMR) AF: 0.0940 AC: 1438 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0888 AC: 308 AN: 3468

East Asian (EAS) AF: 0.117 AC: 607 AN: 5188

South Asian (SAS) AF: 0.105 AC: 508 AN: 4830

European-Finnish (FIN) AF: 0.144 AC: 1529 AN: 10596

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9885 AN: 68024

Other (OTH) AF: 0.119 AC: 252 AN: 2112

Alfa AF: 0.126 Hom.: 2398

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
PhyloP100		0.015

Splicing

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

Other links and lift over

dbSNP: rs12646107; hg19: chr4-174515682;