rs11888095

Variant names:

• chr2-135665214-C-T
• rs11888095
• NM_001378107.1:c.2152+3821C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378107.1(R3HDM1):​c.2152+3821C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,136 control chromosomes in the GnomAD database, including 2,818 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 0.17 (2818 hom., cov: 32)
• Consequence: R3HDM1 NM_001378107.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.527

Genes affected

R3HDM1 (HGNC:9757): (R3H domain containing 1) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

LOC124907893 (HGNC:):

MIR128-1 (HGNC:31510): (microRNA 128-1) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
R3HDM1	NM_001378107.1	c.2152+3821C>T		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+3821C>T		intron_variant	Intron 19 of 26		NM_001378107.1	ENSP00000506980.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25364 AN: 152018 Hom.: 2816 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.0725

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: 0.285

Gnomad NFE AF: 0.0839

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.167 AC: 25391 AN: 152136 Hom.: 2818 Cov.: 32 AF XY: 0.171 AC XY: 12720 AN XY: 74362

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.0839

Gnomad4 OTH AF: 0.168

Alfa AF: 0.116 Hom.: 376

Bravo AF: 0.175

Asia WGS AF: 0.254 AC: 884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.32
DANN	Benign	0.39

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

Publications

LitVar

Other links and lift over

dbSNP: rs11888095; hg19: chr2-136422784;