2-135672287-C-T

Variant names:

• chr2-135672287-C-T
• rs1438303
• NM_001378107.1:c.2153-3045C>T

Variant summary

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

The NM_001378107.1(R3HDM1):​c.2153-3045C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,130 control chromosomes in the GnomAD database, including 3,889 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 0.21 (3889 hom., cov: 32)
• Consequence: R3HDM1 NM_001378107.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06
• Publications: 0 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.43 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	R3HDM1	NM_001378107.1	MANE Select	c.2153-3045C>T		intron	N/A	NP_001365036.1	A0A804HIA8
	R3HDM1	NM_001282798.2		c.2051-3045C>T		intron	N/A	NP_001269727.1	Q15032-3
	R3HDM1	NM_001354200.2		c.2051-3045C>T		intron	N/A	NP_001341129.1	Q15032-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	R3HDM1	ENST00000683871.1	MANE Select	c.2153-3045C>T		intron	N/A	ENSP00000506980.1	A0A804HIA8
	R3HDM1	ENST00000264160.8	TSL:1	c.2048-3045C>T		intron	N/A	ENSP00000264160.4	Q15032-1
	R3HDM1	ENST00000409478.5	TSL:1	c.1664-3045C>T		intron	N/A	ENSP00000386457.1	Q15032-2

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31845 AN: 152012 Hom.: 3880 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.210 AC: 31902 AN: 152130 Hom.: 3889 Cov.: 32 AF XY: 0.216 AC XY: 16039 AN XY: 74378

African (AFR) AF: 0.201 AC: 8328 AN: 41502

American (AMR) AF: 0.292 AC: 4457 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 1628 AN: 3468

East Asian (EAS) AF: 0.445 AC: 2306 AN: 5180

South Asian (SAS) AF: 0.307 AC: 1480 AN: 4818

European-Finnish (FIN) AF: 0.161 AC: 1706 AN: 10588

Middle Eastern (MID) AF: 0.414 AC: 121 AN: 292

European-Non Finnish (NFE) AF: 0.164 AC: 11168 AN: 67984

Other (OTH) AF: 0.276 AC: 583 AN: 2112

Alfa AF: 0.0972 Hom.: 171

Bravo AF: 0.219

Asia WGS AF: 0.375 AC: 1301 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.46
PhyloP100		-2.1
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: rs1438303; hg19: chr2-136429857;