2-135650721-C-T

Variant names:

• chr2-135650721-C-T
• rs4954278
• NM_001378107.1:c.1725+718C>T

Variant summary

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

The ENST00000683871.1(R3HDM1):​c.1725+718C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0915 in 980,812 control chromosomes in the GnomAD database, including 6,433 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 0.16 (2730 hom., cov: 32)
  • Exomes 𝑓: 0.078 (3703 hom.)
• Consequence: R3HDM1 ENST00000683871.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.769
• 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=-0.47).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000683871.1. 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.1725+718C>T		intron	N/A	NP_001365036.1
	R3HDM1	NM_001282798.2		c.1624-1009C>T		intron	N/A	NP_001269727.1
	R3HDM1	NM_001354200.2		c.1624-1009C>T		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.1725+718C>T		intron	N/A	ENSP00000506980.1
	R3HDM1	ENST00000264160.8	TSL:1	c.1624-1012C>T		intron	N/A	ENSP00000264160.4
	R3HDM1	ENST00000409478.5	TSL:1	c.1237-1009C>T		intron	N/A	ENSP00000386457.1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25061 AN: 151896 Hom.: 2731 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.0747

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.280

Gnomad NFE AF: 0.0840

Gnomad OTH AF: 0.166

GnomAD4 exome AF: 0.0780 AC: 64644 AN: 828798 Hom.: 3703 Cov.: 30 AF XY: 0.0781 AC XY: 29898 AN XY: 382892

African (AFR) AF: 0.299 AC: 4687 AN: 15672

American (AMR) AF: 0.204 AC: 199 AN: 974

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 608 AN: 5124

East Asian (EAS) AF: 0.171 AC: 613 AN: 3594

South Asian (SAS) AF: 0.301 AC: 4925 AN: 16382

European-Finnish (FIN) AF: 0.101 AC: 28 AN: 276

Middle Eastern (MID) AF: 0.249 AC: 402 AN: 1612

European-Non Finnish (NFE) AF: 0.0664 AC: 50326 AN: 758000

Other (OTH) AF: 0.105 AC: 2856 AN: 27164

GnomAD4 genome AF: 0.165 AC: 25076 AN: 152014 Hom.: 2730 Cov.: 32 AF XY: 0.169 AC XY: 12581 AN XY: 74300

African (AFR) AF: 0.282 AC: 11687 AN: 41418

American (AMR) AF: 0.211 AC: 3228 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 377 AN: 3468

East Asian (EAS) AF: 0.167 AC: 865 AN: 5172

South Asian (SAS) AF: 0.320 AC: 1541 AN: 4822

European-Finnish (FIN) AF: 0.110 AC: 1164 AN: 10560

Middle Eastern (MID) AF: 0.277 AC: 81 AN: 292

European-Non Finnish (NFE) AF: 0.0840 AC: 5714 AN: 67988

Other (OTH) AF: 0.166 AC: 351 AN: 2114

Alfa AF: 0.111 Hom.: 2247

Bravo AF: 0.173

Asia WGS AF: 0.253 AC: 880 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	8.6
DANN	Benign	0.81
PhyloP100		0.77
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs4954278; hg19: chr2-136408291;