rs2304368

Variant names:

• chr2-135709989-C-A
• rs2304368
• NM_001378107.1:c.2564-70C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-135709989-C-A
• chr2-135709989-C-T

Variant summary

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

The NM_001378107.1(R3HDM1):​c.2564-70C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0308 in 1,436,632 control chromosomes in the GnomAD database, including 2,006 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 0.076 (932 hom., cov: 33)
  • Exomes 𝑓: 0.025 (1074 hom.)
• Consequence: R3HDM1 NM_001378107.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.241
• Publications: 5 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
R3HDM1	NM_001378107.1	c.2564-70C>A		intron_variant	Intron 22 of 26	ENST00000683871.1	NP_001365036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
R3HDM1	ENST00000683871.1	c.2564-70C>A		intron_variant	Intron 22 of 26		NM_001378107.1	ENSP00000506980.1

Frequencies

GnomAD3 genomes AF: 0.0759 AC: 11540 AN: 152068 Hom.: 928 Cov.: 33

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0455

Gnomad ASJ AF: 0.0513

Gnomad EAS AF: 0.0574

Gnomad SAS AF: 0.0150

Gnomad FIN AF: 0.0135

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0239

Gnomad OTH AF: 0.0647

GnomAD4 exome AF: 0.0254 AC: 32660 AN: 1284446 Hom.: 1074 AF XY: 0.0254 AC XY: 16236 AN XY: 638806

African (AFR) AF: 0.205 AC: 5962 AN: 29072

American (AMR) AF: 0.0433 AC: 1472 AN: 33958

Ashkenazi Jewish (ASJ) AF: 0.0524 AC: 1117 AN: 21318

East Asian (EAS) AF: 0.0522 AC: 2017 AN: 38622

South Asian (SAS) AF: 0.0155 AC: 1118 AN: 72016

European-Finnish (FIN) AF: 0.0162 AC: 779 AN: 48058

Middle Eastern (MID) AF: 0.0417 AC: 217 AN: 5208

European-Non Finnish (NFE) AF: 0.0184 AC: 18023 AN: 982084

Other (OTH) AF: 0.0361 AC: 1955 AN: 54110

GnomAD4 genome AF: 0.0760 AC: 11566 AN: 152186 Hom.: 932 Cov.: 33 AF XY: 0.0733 AC XY: 5452 AN XY: 74408

African (AFR) AF: 0.203 AC: 8406 AN: 41506

American (AMR) AF: 0.0455 AC: 696 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0513 AC: 178 AN: 3470

East Asian (EAS) AF: 0.0576 AC: 298 AN: 5176

South Asian (SAS) AF: 0.0148 AC: 71 AN: 4806

European-Finnish (FIN) AF: 0.0135 AC: 143 AN: 10606

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0239 AC: 1625 AN: 68022

Other (OTH) AF: 0.0650 AC: 137 AN: 2108

Alfa AF: 0.0668 Hom.: 128

Bravo AF: 0.0848

Asia WGS AF: 0.0380 AC: 134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.9
DANN	Benign	0.33
PhyloP100		0.24
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: rs2304368; hg19: chr2-136467559;