chr4-173653255-C-G

Position:

• chr4-173653255-C-G

Variant summary

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

The ENST00000647106.1(HAND2-AS1):​n.276-5464C>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 0.0755 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, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.661

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=-0.84).
• 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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAND2-AS1	ENST00000647106.1	n.276-5464C>G		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.0503

Gnomad4 AMR AF: 0.0686

Gnomad4 ASJ AF: 0.0752

Gnomad4 EAS AF: 0.0779

Gnomad4 SAS AF: 0.0997

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.0813

Gnomad4 OTH AF: 0.0810

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11723864; hg19: chr4-174574406;