2-135662391-A-G

Variant names:

• chr2-135662391-A-G
• rs1446584
• NM_001378107.1:c.2152+998A>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.2152+998A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 152,100 control chromosomes in the GnomAD database, including 23,075 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 0.49 (23075 hom., cov: 32)
• Consequence: R3HDM1 NM_001378107.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800
• Publications: 12 publications found

Genes affected

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

LOC124907893 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.856 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.2152+998A>G		intron	N/A	NP_001365036.1
	R3HDM1	NM_001282798.2		c.2050+998A>G		intron	N/A	NP_001269727.1
	R3HDM1	NM_001354200.2		c.2050+998A>G		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.2152+998A>G		intron	N/A	ENSP00000506980.1
	R3HDM1	ENST00000264160.8	TSL:1	c.2047+998A>G		intron	N/A	ENSP00000264160.4
	R3HDM1	ENST00000409478.5	TSL:1	c.1663+998A>G		intron	N/A	ENSP00000386457.1

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74628 AN: 151982 Hom.: 23016 Cov.: 32

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.877

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.491 AC: 74750 AN: 152100 Hom.: 23075 Cov.: 32 AF XY: 0.503 AC XY: 37366 AN XY: 74360

African (AFR) AF: 0.781 AC: 32390 AN: 41494

American (AMR) AF: 0.595 AC: 9089 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2270 AN: 3470

East Asian (EAS) AF: 0.877 AC: 4536 AN: 5170

South Asian (SAS) AF: 0.686 AC: 3304 AN: 4818

European-Finnish (FIN) AF: 0.285 AC: 3018 AN: 10574

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18591 AN: 67988

Other (OTH) AF: 0.540 AC: 1139 AN: 2110

Alfa AF: 0.395 Hom.: 4658

Bravo AF: 0.524

Asia WGS AF: 0.780 AC: 2711 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.9
DANN	Benign	0.68
PhyloP100		0.0080
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: rs1446584; hg19: chr2-136419961;