rs2289963

Variant names:

• chr2-135648308-G-A
• rs2289963
• NM_001378107.1:c.1624-1594G>A

Variant summary

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

The NM_001378107.1(R3HDM1):​c.1624-1594G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 151,928 control chromosomes in the GnomAD database, including 1,357 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 0.12 (1357 hom., cov: 32)
• Consequence: R3HDM1 NM_001378107.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.04
• Publications: 0 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
R3HDM1	NM_001378107.1	c.1624-1594G>A		intron_variant	Intron 16 of 26	ENST00000683871.1	NP_001365036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
R3HDM1	ENST00000683871.1	c.1624-1594G>A		intron_variant	Intron 16 of 26		NM_001378107.1	ENSP00000506980.1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18480 AN: 151810 Hom.: 1361 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.0841

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.122 AC: 18490 AN: 151928 Hom.: 1357 Cov.: 32 AF XY: 0.128 AC XY: 9539 AN XY: 74246

African (AFR) AF: 0.130 AC: 5400 AN: 41438

American (AMR) AF: 0.196 AC: 2997 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 382 AN: 3468

East Asian (EAS) AF: 0.168 AC: 871 AN: 5182

South Asian (SAS) AF: 0.316 AC: 1521 AN: 4816

European-Finnish (FIN) AF: 0.111 AC: 1161 AN: 10492

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.0841 AC: 5713 AN: 67952

Other (OTH) AF: 0.140 AC: 295 AN: 2106

Alfa AF: 0.107 Hom.: 277

Bravo AF: 0.124

Asia WGS AF: 0.248 AC: 860 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.019
DANN	Benign	0.68
PhyloP100		-3.0
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: rs2289963; hg19: chr2-136405878;