chr2-135681947-A-C

Variant names:

• chr2-135681947-A-C
• rs313519
• NM_001378107.1:c.2459+1623A>C

Variant summary

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

The NM_001378107.1(R3HDM1):​c.2459+1623A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 151,244 control chromosomes in the GnomAD database, including 24,106 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 0.50 (24106 hom., cov: 29)
• Consequence: R3HDM1 NM_001378107.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 10 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.856 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	R3HDM1	NM_001378107.1	MANE Select	c.2459+1623A>C		intron	N/A	NP_001365036.1
	R3HDM1	NM_001282798.2		c.2357+1623A>C		intron	N/A	NP_001269727.1
	R3HDM1	NM_001354200.2		c.2357+1623A>C		intron	N/A	NP_001341129.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	R3HDM1	ENST00000683871.1	MANE Select	c.2459+1623A>C		intron	N/A	ENSP00000506980.1
	R3HDM1	ENST00000264160.8	TSL:1	c.2354+1623A>C		intron	N/A	ENSP00000264160.4
	R3HDM1	ENST00000409478.5	TSL:1	c.1970+1623A>C		intron	N/A	ENSP00000386457.1

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75611 AN: 151126 Hom.: 24043 Cov.: 29

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.877

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.540

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

GnomAD4 genome AF: 0.501 AC: 75736 AN: 151244 Hom.: 24106 Cov.: 29 AF XY: 0.512 AC XY: 37778 AN XY: 73830

African (AFR) AF: 0.816 AC: 33582 AN: 41168

American (AMR) AF: 0.598 AC: 9058 AN: 15146

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 2260 AN: 3460

East Asian (EAS) AF: 0.877 AC: 4512 AN: 5144

South Asian (SAS) AF: 0.686 AC: 3260 AN: 4752

European-Finnish (FIN) AF: 0.284 AC: 2947 AN: 10394

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18559 AN: 67880

Other (OTH) AF: 0.546 AC: 1148 AN: 2104

Alfa AF: 0.360 Hom.: 7560

Bravo AF: 0.536

Asia WGS AF: 0.781 AC: 2715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.36
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs313519; hg19: chr2-136439517;