chr3-49995795-T-C

Variant names:

• chr3-49995795-T-C
• rs17657688
• NM_005777.3:c.1484-3645T>C

Variant summary

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

The NM_005777.3(RBM6):​c.1484-3645T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 151,994 control chromosomes in the GnomAD database, including 12,044 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 0.39 (12044 hom., cov: 31)
• Consequence: RBM6 NM_005777.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520
• Publications: 18 publications found

Genes affected

RBM6 (HGNC:9903): (RNA binding motif protein 6) Enables RNA binding activity. Predicted to be involved in mRNA splicing, via spliceosome. Predicted to be active 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 (NFE) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM6	NM_005777.3	c.1484-3645T>C		intron_variant	Intron 5 of 20	ENST00000266022.9	NP_005768.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM6	ENST00000266022.9	c.1484-3645T>C		intron_variant	Intron 5 of 20	1	NM_005777.3	ENSP00000266022.4

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59214 AN: 151876 Hom.: 12035 Cov.: 31

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.390 AC: 59243 AN: 151994 Hom.: 12044 Cov.: 31 AF XY: 0.380 AC XY: 28238 AN XY: 74278

African (AFR) AF: 0.398 AC: 16479 AN: 41430

American (AMR) AF: 0.336 AC: 5133 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1114 AN: 3472

East Asian (EAS) AF: 0.115 AC: 598 AN: 5184

South Asian (SAS) AF: 0.172 AC: 829 AN: 4822

European-Finnish (FIN) AF: 0.383 AC: 4046 AN: 10554

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.437 AC: 29712 AN: 67946

Other (OTH) AF: 0.391 AC: 825 AN: 2110

Alfa AF: 0.407 Hom.: 2649

Bravo AF: 0.393

Asia WGS AF: 0.211 AC: 734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.7
DANN	Benign	0.73
PhyloP100		0.052
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: rs17657688; hg19: chr3-50033228;