rs11614506

Variant names:

• chr12-57421892-T-C
• rs11614506
• NM_001394031.1:c.-106+8828A>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.-106+8828A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 151,666 control chromosomes in the GnomAD database, including 2,673 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 (2673 hom., cov: 29)
• Consequence: R3HDM2 NM_001394031.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118
• Publications: 9 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
R3HDM2	NM_001394031.1	c.-106+8828A>G		intron_variant	Intron 1 of 23	ENST00000402412.6	NP_001380960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
R3HDM2	ENST00000402412.6	c.-106+8828A>G		intron_variant	Intron 1 of 23	1	NM_001394031.1	ENSP00000385839.1
R3HDM2	ENST00000347140.7	c.-106+8828A>G		intron_variant	Intron 1 of 23	1		ENSP00000317903.6
R3HDM2	ENST00000448732.1	c.-36+8828A>G		intron_variant	Intron 1 of 1	1		ENSP00000405777.1
R3HDM2	ENST00000634871.1	c.-106+8828A>G		intron_variant	Intron 1 of 23	5		ENSP00000489424.1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24667 AN: 151550 Hom.: 2663 Cov.: 29

Gnomad AFR AF: 0.0402

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.0933

Gnomad SAS AF: 0.0809

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.163 AC: 24684 AN: 151666 Hom.: 2673 Cov.: 29 AF XY: 0.161 AC XY: 11958 AN XY: 74100

African (AFR) AF: 0.0401 AC: 1660 AN: 41372

American (AMR) AF: 0.271 AC: 4123 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 537 AN: 3466

East Asian (EAS) AF: 0.0929 AC: 478 AN: 5146

South Asian (SAS) AF: 0.0808 AC: 388 AN: 4800

European-Finnish (FIN) AF: 0.221 AC: 2323 AN: 10506

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14645 AN: 67852

Other (OTH) AF: 0.158 AC: 333 AN: 2110

Alfa AF: 0.188 Hom.: 410

Bravo AF: 0.169

Asia WGS AF: 0.0970 AC: 339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.7
DANN	Benign	0.78
PhyloP100		0.12
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: rs11614506; hg19: chr12-57815675;