rs11723864

Variant names:

• chr4-173653255-C-G
• rs11723864
• ENST00000647106.1:n.276-5464C>G

Variant summary

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

The ENST00000647106.1(HAND2-AS1):​n.276-5464C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0755 in 152,174 control chromosomes in the GnomAD database, including 503 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 0.076 (503 hom., cov: 32)
• Consequence: HAND2-AS1 ENST00000647106.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.661
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0924 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.276-5464C>G		intron_variant	Intron 2 of 2
HAND2-AS1	ENST00000829139.1	n.227-43355C>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0756 AC: 11492 AN: 152056 Hom.: 504 Cov.: 32

Gnomad AFR AF: 0.0504

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0686

Gnomad ASJ AF: 0.0752

Gnomad EAS AF: 0.0773

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0813

Gnomad OTH AF: 0.0814

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

GnomAD4 genome AF: 0.0755 AC: 11491 AN: 152174 Hom.: 503 Cov.: 32 AF XY: 0.0787 AC XY: 5852 AN XY: 74398

African (AFR) AF: 0.0503 AC: 2090 AN: 41528

American (AMR) AF: 0.0686 AC: 1049 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0752 AC: 261 AN: 3472

East Asian (EAS) AF: 0.0779 AC: 403 AN: 5174

South Asian (SAS) AF: 0.0997 AC: 481 AN: 4824

European-Finnish (FIN) AF: 0.137 AC: 1454 AN: 10580

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0813 AC: 5528 AN: 67992

Other (OTH) AF: 0.0810 AC: 171 AN: 2110

Alfa AF: 0.0729 Hom.: 57

Bravo AF: 0.0680

Asia WGS AF: 0.0710 AC: 247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.88
DANN	Benign	0.32
PhyloP100		-0.66

Splicing

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

Other links and lift over

dbSNP: rs11723864; hg19: chr4-174574406;