chr2-135623778-G-A

Variant names:

• chr2-135623778-G-A
• rs12465802
• NM_001378107.1:c.497+1046G>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.497+1046G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 152,094 control chromosomes in the GnomAD database, including 33,467 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 0.61 (33467 hom., cov: 32)
• Consequence: R3HDM1 NM_001378107.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.826
• Publications: 18 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 (EAS) allele frequency at 95% confidence interval = 0.975 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.497+1046G>A		intron	N/A	NP_001365036.1
	R3HDM1	NM_001282798.2		c.497+1046G>A		intron	N/A	NP_001269727.1
	R3HDM1	NM_001354200.2		c.497+1046G>A		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.497+1046G>A		intron	N/A	ENSP00000506980.1
	R3HDM1	ENST00000264160.8	TSL:1	c.497+1046G>A		intron	N/A	ENSP00000264160.4
	R3HDM1	ENST00000409478.5	TSL:1	c.365+1046G>A		intron	N/A	ENSP00000386457.1

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92327 AN: 151976 Hom.: 33401 Cov.: 32

Gnomad AFR AF: 0.880

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.778

Gnomad ASJ AF: 0.872

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.824

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.705

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

GnomAD4 genome AF: 0.608 AC: 92457 AN: 152094 Hom.: 33467 Cov.: 32 AF XY: 0.623 AC XY: 46352 AN XY: 74366

African (AFR) AF: 0.880 AC: 36560 AN: 41522

American (AMR) AF: 0.779 AC: 11901 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.872 AC: 3025 AN: 3470

East Asian (EAS) AF: 0.998 AC: 5173 AN: 5184

South Asian (SAS) AF: 0.823 AC: 3972 AN: 4824

European-Finnish (FIN) AF: 0.426 AC: 4502 AN: 10566

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.372 AC: 25296 AN: 67932

Other (OTH) AF: 0.708 AC: 1493 AN: 2108

Alfa AF: 0.532 Hom.: 44866

Bravo AF: 0.646

Asia WGS AF: 0.924 AC: 3210 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	0.067
DANN	Benign	0.18
PhyloP100		-0.83
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: rs12465802; hg19: chr2-136381348;