3-50055776-G-A

Variant names:

• chr3-50055776-G-A
• rs6762477
• NM_005777.3:c.1693+1381G>A

Variant summary

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

The NM_005777.3(RBM6):​c.1693+1381G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 152,064 control chromosomes in the GnomAD database, including 32,324 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 0.65 (32324 hom., cov: 32)
• Consequence: RBM6 NM_005777.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.229
• Publications: 56 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005777.3. 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
	RBM6	NM_005777.3	MANE Select	c.1693+1381G>A		intron	N/A	NP_005768.1
	RBM6	NM_001349194.2		c.151+1381G>A		intron	N/A	NP_001336123.1
	RBM6	NM_001167582.2		c.127+1381G>A		intron	N/A	NP_001161054.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM6	ENST00000266022.9	TSL:1 MANE Select	c.1693+1381G>A		intron	N/A	ENSP00000266022.4
	RBM6	ENST00000442092.5	TSL:1	c.127+1381G>A		intron	N/A	ENSP00000393530.1
	RBM6	ENST00000443081.5	TSL:5	c.1297+1381G>A		intron	N/A	ENSP00000396466.1

Frequencies

GnomAD3 genomes AF: 0.645 AC: 98060 AN: 151946 Hom.: 32278 Cov.: 32

Gnomad AFR AF: 0.727

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.632

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

GnomAD4 genome AF: 0.646 AC: 98160 AN: 152064 Hom.: 32324 Cov.: 32 AF XY: 0.654 AC XY: 48630 AN XY: 74326

African (AFR) AF: 0.727 AC: 30162 AN: 41474

American (AMR) AF: 0.674 AC: 10290 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2377 AN: 3468

East Asian (EAS) AF: 0.884 AC: 4584 AN: 5186

South Asian (SAS) AF: 0.828 AC: 3997 AN: 4828

European-Finnish (FIN) AF: 0.614 AC: 6470 AN: 10546

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.563 AC: 38255 AN: 67976

Other (OTH) AF: 0.629 AC: 1329 AN: 2112

Alfa AF: 0.596 Hom.: 72838

Bravo AF: 0.648

Asia WGS AF: 0.797 AC: 2772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.89
DANN	Benign	0.50
PhyloP100		-0.23
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: rs6762477; hg19: chr3-50093209;