2-135566655-A-G

Variant names:

• chr2-135566655-A-G
• rs4954265
• NM_001378107.1:c.-250+35022A>G

Variant summary

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

The NM_001378107.1(R3HDM1):​c.-250+35022A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 749,052 control chromosomes in the GnomAD database, including 13,156 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 0.26 (8817 hom., cov: 32)
  • Exomes 𝑓: 0.079 (4339 hom.)
• Consequence: R3HDM1 NM_001378107.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.435
• Publications: 9 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.593 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.-250+35022A>G		intron	N/A	NP_001365036.1
	R3HDM1	NM_001354200.2		c.-250+35022A>G		intron	N/A	NP_001341129.1
	R3HDM1	NM_015361.4		c.-250+35022A>G		intron	N/A	NP_056176.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	R3HDM1	ENST00000683871.1	MANE Select	c.-250+35022A>G		intron	N/A	ENSP00000506980.1
	R3HDM1	ENST00000264160.8	TSL:1	c.-250+35022A>G		intron	N/A	ENSP00000264160.4
	R3HDM1	ENST00000409478.5	TSL:1	c.-250+35022A>G		intron	N/A	ENSP00000386457.1

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38907 AN: 151958 Hom.: 8788 Cov.: 32

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.0745

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.0831

Gnomad OTH AF: 0.225

GnomAD4 exome AF: 0.0789 AC: 47125 AN: 596976 Hom.: 4339 Cov.: 8 AF XY: 0.0788 AC XY: 22024 AN XY: 279482

African (AFR) AF: 0.635 AC: 6900 AN: 10858

American (AMR) AF: 0.225 AC: 156 AN: 694

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 646 AN: 3690

East Asian (EAS) AF: 0.212 AC: 553 AN: 2608

South Asian (SAS) AF: 0.300 AC: 3477 AN: 11582

European-Finnish (FIN) AF: 0.0817 AC: 17 AN: 208

Middle Eastern (MID) AF: 0.222 AC: 264 AN: 1188

European-Non Finnish (NFE) AF: 0.0597 AC: 32660 AN: 546652

Other (OTH) AF: 0.126 AC: 2452 AN: 19496

GnomAD4 genome AF: 0.256 AC: 38987 AN: 152076 Hom.: 8817 Cov.: 32 AF XY: 0.257 AC XY: 19116 AN XY: 74356

African (AFR) AF: 0.599 AC: 24801 AN: 41388

American (AMR) AF: 0.254 AC: 3881 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 540 AN: 3468

East Asian (EAS) AF: 0.220 AC: 1142 AN: 5184

South Asian (SAS) AF: 0.330 AC: 1591 AN: 4820

European-Finnish (FIN) AF: 0.0745 AC: 790 AN: 10604

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.0831 AC: 5653 AN: 68028

Other (OTH) AF: 0.227 AC: 479 AN: 2114

Alfa AF: 0.151 Hom.: 11187

Bravo AF: 0.281

Asia WGS AF: 0.309 AC: 1075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	12
DANN	Benign	0.77
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4954265; hg19: chr2-136324225;