chr12-57372609-G-C

Variant names:

• chr12-57372609-G-C
• rs4760254
• NM_001394031.1:c.-36+23140C>G

Variant summary

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

The NM_001394031.1(R3HDM2):​c.-36+23140C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,082 control chromosomes in the GnomAD database, including 3,111 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 0.19 (3111 hom., cov: 32)
• Consequence: R3HDM2 NM_001394031.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.315
• Publications: 10 publications found

Genes affected

R3HDM2 (HGNC:29167): (R3H domain containing 2) Enables RNA binding activity. Predicted to be located in nucleus. [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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394031.1. 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
	R3HDM2	NM_001394031.1	MANE Select	c.-36+23140C>G		intron	N/A	NP_001380960.1
	R3HDM2	NM_001351204.2		c.-36+23140C>G		intron	N/A	NP_001338133.1
	R3HDM2	NM_001351207.2		c.-36+23140C>G		intron	N/A	NP_001338136.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	R3HDM2	ENST00000402412.6	TSL:1 MANE Select	c.-36+23140C>G		intron	N/A	ENSP00000385839.1
	R3HDM2	ENST00000347140.7	TSL:1	c.-36+23140C>G		intron	N/A	ENSP00000317903.6
	R3HDM2	ENST00000448732.1	TSL:1	c.-36+58111C>G		intron	N/A	ENSP00000405777.1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28346 AN: 151964 Hom.: 3100 Cov.: 32

Gnomad AFR AF: 0.0955

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.100

Gnomad SAS AF: 0.0931

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.187 AC: 28370 AN: 152082 Hom.: 3111 Cov.: 32 AF XY: 0.184 AC XY: 13697 AN XY: 74322

African (AFR) AF: 0.0954 AC: 3960 AN: 41494

American (AMR) AF: 0.279 AC: 4261 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 554 AN: 3470

East Asian (EAS) AF: 0.0997 AC: 517 AN: 5184

South Asian (SAS) AF: 0.0927 AC: 447 AN: 4820

European-Finnish (FIN) AF: 0.229 AC: 2416 AN: 10564

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15641 AN: 67968

Other (OTH) AF: 0.173 AC: 365 AN: 2108

Alfa AF: 0.107 Hom.: 175

Bravo AF: 0.194

Asia WGS AF: 0.115 AC: 403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.59
PhyloP100		0.32
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: rs4760254; hg19: chr12-57766392;