chr2-135663120-A-G

Variant names:

• chr2-135663120-A-G
• rs4954280
• NM_001378107.1:c.2152+1727A>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+1727A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 146,722 control chromosomes in the GnomAD database, including 22,063 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 (22063 hom., cov: 23)
• Consequence: R3HDM1 NM_001378107.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.268
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
R3HDM1	NM_001378107.1	c.2152+1727A>G		intron_variant	Intron 19 of 26	ENST00000683871.1	NP_001365036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
R3HDM1	ENST00000683871.1	c.2152+1727A>G		intron_variant	Intron 19 of 26		NM_001378107.1	ENSP00000506980.1

Frequencies

GnomAD3 genomes AF: 0.487 AC: 71451 AN: 146642 Hom.: 22016 Cov.: 23

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.488 AC: 71542 AN: 146722 Hom.: 22063 Cov.: 23 AF XY: 0.499 AC XY: 35590 AN XY: 71280

African (AFR) AF: 0.781 AC: 30906 AN: 39556

American (AMR) AF: 0.593 AC: 8614 AN: 14534

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2246 AN: 3436

East Asian (EAS) AF: 0.880 AC: 4337 AN: 4930

South Asian (SAS) AF: 0.686 AC: 3173 AN: 4626

European-Finnish (FIN) AF: 0.267 AC: 2487 AN: 9316

Middle Eastern (MID) AF: 0.745 AC: 204 AN: 274

European-Non Finnish (NFE) AF: 0.272 AC: 18291 AN: 67124

Other (OTH) AF: 0.540 AC: 1091 AN: 2022

Alfa AF: 0.343 Hom.: 3045

Bravo AF: 0.524

Asia WGS AF: 0.780 AC: 2709 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.3
DANN	Benign	0.39
PhyloP100		0.27
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: rs4954280; hg19: chr2-136420690;