rs11888095

Variant names:

• chr2-135665214-C-T
• rs11888095
• NM_001378107.1:c.2152+3821C>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.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
• Publications: 15 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:):

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

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	R3HDM1	NM_001378107.1	MANE Select	c.2152+3821C>T		intron	N/A	NP_001365036.1
	R3HDM1	NM_001282798.2		c.2050+3821C>T		intron	N/A	NP_001269727.1
	R3HDM1	NM_001354200.2		c.2050+3821C>T		intron	N/A	NP_001341129.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	R3HDM1	ENST00000683871.1	MANE Select	c.2152+3821C>T		intron	N/A	ENSP00000506980.1
	R3HDM1	ENST00000264160.8	TSL:1	c.2047+3821C>T		intron	N/A	ENSP00000264160.4
	R3HDM1	ENST00000409478.5	TSL:1	c.1663+3821C>T		intron	N/A	ENSP00000386457.1

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

African (AFR) AF: 0.289 AC: 12000 AN: 41474

American (AMR) AF: 0.212 AC: 3232 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 377 AN: 3468

East Asian (EAS) AF: 0.168 AC: 867 AN: 5174

South Asian (SAS) AF: 0.319 AC: 1540 AN: 4822

European-Finnish (FIN) AF: 0.110 AC: 1162 AN: 10584

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.0839 AC: 5709 AN: 68016

Other (OTH) AF: 0.168 AC: 355 AN: 2114

Alfa AF: 0.118 Hom.: 402

Bravo AF: 0.175

Asia WGS AF: 0.254 AC: 884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.32
DANN	Benign	0.39
PhyloP100		-0.53
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: rs11888095; hg19: chr2-136422784;