chr2-135709594-C-A

Variant names:

• chr2-135709594-C-A
• rs2304367
• NM_001378107.1:c.2563+58C>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.2563+58C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.992 in 1,586,016 control chromosomes in the GnomAD database, including 780,208 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 0.97 (71883 hom., cov: 31)
  • Exomes 𝑓: 0.99 (708325 hom.)
• Consequence: R3HDM1 NM_001378107.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.289
• Publications: 7 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
R3HDM1	NM_001378107.1	c.2563+58C>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.2563+58C>A		intron_variant	Intron 22 of 26		NM_001378107.1	ENSP00000506980.1

Frequencies

GnomAD3 genomes AF: 0.971 AC: 147720 AN: 152184 Hom.: 71832 Cov.: 31

Gnomad AFR AF: 0.907

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.985

Gnomad ASJ AF: 0.985

Gnomad EAS AF: 0.983

Gnomad SAS AF: 0.966

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.979

GnomAD4 exome AF: 0.994 AC: 1424908 AN: 1433714 Hom.: 708325 AF XY: 0.993 AC XY: 708128 AN XY: 712916

African (AFR) AF: 0.899 AC: 29004 AN: 32276

American (AMR) AF: 0.994 AC: 40365 AN: 40608

Ashkenazi Jewish (ASJ) AF: 0.979 AC: 24763 AN: 25306

East Asian (EAS) AF: 0.975 AC: 38265 AN: 39266

South Asian (SAS) AF: 0.969 AC: 81202 AN: 83826

European-Finnish (FIN) AF: 1.00 AC: 52954 AN: 52954

Middle Eastern (MID) AF: 0.991 AC: 5628 AN: 5678

European-Non Finnish (NFE) AF: 1.00 AC: 1094065 AN: 1094500

Other (OTH) AF: 0.989 AC: 58662 AN: 59300

GnomAD4 genome AF: 0.971 AC: 147830 AN: 152302 Hom.: 71883 Cov.: 31 AF XY: 0.970 AC XY: 72246 AN XY: 74478

African (AFR) AF: 0.907 AC: 37688 AN: 41542

American (AMR) AF: 0.985 AC: 15072 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.985 AC: 3417 AN: 3468

East Asian (EAS) AF: 0.983 AC: 5090 AN: 5180

South Asian (SAS) AF: 0.966 AC: 4666 AN: 4828

European-Finnish (FIN) AF: 1.00 AC: 10618 AN: 10618

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 68002 AN: 68038

Other (OTH) AF: 0.980 AC: 2071 AN: 2114

Alfa AF: 0.979 Hom.: 23447

Bravo AF: 0.967

Asia WGS AF: 0.962 AC: 3347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
DANN	Benign	0.65
PhyloP100		0.29
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: rs2304367; hg19: chr2-136467164;