2-135649909-A-G

Variant names:

• chr2-135649909-A-G
• rs1446585
• NM_001378107.1:c.1631A>G

Variant summary

Our verdict is Benign. The variant received -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. 6/6 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
• Publications: 48 publications found

Genes affected

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

ENSG00000308733 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378107.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	R3HDM1	NM_001378107.1	MANE Select	c.1631A>G	p.His544Arg	missense	Exon 17 of 27	NP_001365036.1	A0A804HIA8
	R3HDM1	NM_001282798.2		c.1624-1821A>G		intron	N/A	NP_001269727.1	Q15032-3
	R3HDM1	NM_001354200.2		c.1624-1821A>G		intron	N/A	NP_001341129.1	Q15032-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	R3HDM1	ENST00000683871.1	MANE Select	c.1631A>G	p.His544Arg	missense	Exon 17 of 27	ENSP00000506980.1	A0A804HIA8
	R3HDM1	ENST00000264160.8	TSL:1	c.1624-1824A>G		intron	N/A	ENSP00000264160.4	Q15032-1
	R3HDM1	ENST00000409478.5	TSL:1	c.1237-1821A>G		intron	N/A	ENSP00000386457.1	Q15032-2

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

GnomAD2 exomes AF: 0.565 AC: 74929 AN: 132564 AF XY: 0.560

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 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

African (AFR) AF: 0.914 AC: 21141 AN: 23140

American (AMR) AF: 0.741 AC: 17877 AN: 24136

Ashkenazi Jewish (ASJ) AF: 0.848 AC: 12382 AN: 14606

East Asian (EAS) AF: 0.998 AC: 11616 AN: 11644

South Asian (SAS) AF: 0.715 AC: 47852 AN: 66964

European-Finnish (FIN) AF: 0.349 AC: 9097 AN: 26036

Middle Eastern (MID) AF: 0.915 AC: 3872 AN: 4232

European-Non Finnish (NFE) AF: 0.252 AC: 226143 AN: 896806

Other (OTH) AF: 0.448 AC: 17761 AN: 39624

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

African (AFR) AF: 0.874 AC: 36268 AN: 41502

American (AMR) AF: 0.714 AC: 10910 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.837 AC: 2905 AN: 3470

East Asian (EAS) AF: 0.997 AC: 5164 AN: 5182

South Asian (SAS) AF: 0.773 AC: 3724 AN: 4820

European-Finnish (FIN) AF: 0.358 AC: 3785 AN: 10558

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22850 AN: 67956

Other (OTH) AF: 0.666 AC: 1407 AN: 2114

Alfa AF: 0.455 Hom.: 34702

Bravo AF: 0.613

Asia WGS AF: 0.902 AC: 3134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_noAF	Benign	-0.18
CADD	Benign	16
DANN	Benign	0.83
PhyloP100		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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