2-135649909-A-G

Position:

• chr2-135649909-A-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4 BA1

The NM_001378107.1(R3HDM1):​c.1631A>G​(p.His544Arg) variant causes a missense change. The variant allele was found at a frequency of 0.362 in 1,259,270 control chromosomes in the GnomAD database, including 116,810 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.58 (30871 hom., cov: 32)
  • Exomes 𝑓: 0.33 (85939 hom.)
• Consequence: R3HDM1 NM_001378107.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.66

Genes affected

R3HDM1 (HGNC:9757): (R3H domain containing 1) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.18).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
R3HDM1	NM_001378107.1	c.1631A>G	p.His544Arg	missense_variant	17/27	ENST00000683871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
R3HDM1	ENST00000683871.1	c.1631A>G	p.His544Arg	missense_variant	17/27		NM_001378107.1	A1

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87396 AN: 151964 Hom.: 30808 Cov.: 32

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.837

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.773

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.662

GnomAD3 exomes AF: 0.565 AC: 74929 AN: 132564 Hom.: 25805 AF XY: 0.560 AC XY: 40323 AN XY: 71990

Gnomad AFR exome AF: 0.891

Gnomad AMR exome AF: 0.741

Gnomad ASJ exome AF: 0.849

Gnomad EAS exome AF: 0.999

Gnomad SAS exome AF: 0.715

Gnomad FIN exome AF: 0.354

Gnomad NFE exome AF: 0.332

Gnomad OTH exome AF: 0.596

GnomAD4 exome AF: 0.332 AC: 367741 AN: 1107188 Hom.: 85939 Cov.: 30 AF XY: 0.347 AC XY: 187774 AN XY: 541244

Gnomad4 AFR exome AF: 0.914

Gnomad4 AMR exome AF: 0.741

Gnomad4 ASJ exome AF: 0.848

Gnomad4 EAS exome AF: 0.998

Gnomad4 SAS exome AF: 0.715

Gnomad4 FIN exome AF: 0.349

Gnomad4 NFE exome AF: 0.252

Gnomad4 OTH exome AF: 0.448

GnomAD4 genome AF: 0.575 AC: 87523 AN: 152082 Hom.: 30871 Cov.: 32 AF XY: 0.589 AC XY: 43772 AN XY: 74330

Gnomad4 AFR AF: 0.874

Gnomad4 AMR AF: 0.714

Gnomad4 ASJ AF: 0.837

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.773

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.666

Alfa AF: 0.424 Hom.: 19744

Bravo AF: 0.613

Asia WGS AF: 0.902 AC: 3134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.18
CADD	Benign	16
DANN	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1446585; hg19: chr2-136407479; COSMIC: COSV51520989; COSMIC: COSV51520989;