4-173633681-A-G

Variant names:

• chr4-173633681-A-G
• rs11944332

Variant summary

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

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: RANP6 intragenic
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85
• Publications: 3 publications found

Genes affected

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

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=-0.58).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000647106.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAND2-AS1	ENST00000647106.1		n.142-930A>G		intron	N/A
	HAND2-AS1	ENST00000829139.1		n.226+24470A>G		intron	N/A
	HAND2-AS1	ENST00000829140.1		n.388-930A>G		intron	N/A

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

African (AFR) AF: 0.101 AC: 1716 AN: 16922

American (AMR) AF: 0.0650 AC: 2181 AN: 33552

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 2048 AN: 16392

East Asian (EAS) AF: 0.00565 AC: 187 AN: 33116

South Asian (SAS) AF: 0.132 AC: 7943 AN: 60196

European-Finnish (FIN) AF: 0.107 AC: 4518 AN: 42276

Middle Eastern (MID) AF: 0.121 AC: 348 AN: 2886

European-Non Finnish (NFE) AF: 0.132 AC: 52421 AN: 398532

Other (OTH) AF: 0.119 AC: 3746 AN: 31356

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

African (AFR) AF: 0.102 AC: 4229 AN: 41542

American (AMR) AF: 0.0822 AC: 1257 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 464 AN: 3472

East Asian (EAS) AF: 0.00676 AC: 35 AN: 5176

South Asian (SAS) AF: 0.122 AC: 590 AN: 4818

European-Finnish (FIN) AF: 0.108 AC: 1148 AN: 10596

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9145 AN: 67994

Other (OTH) AF: 0.113 AC: 238 AN: 2114

Alfa AF: 0.122 Hom.: 136

Bravo AF: 0.111

Asia WGS AF: 0.0680 AC: 237 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	7.2
DANN	Benign	0.67
PhyloP100		1.9

Splicing

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

Other links and lift over

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