rs6794945

Positions:

• chr3-133799619-C-T

Variant summary

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

The ENST00000650377.1(ENSG00000285908):​n.3122G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 151,874 control chromosomes in the GnomAD database, including 6,468 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 0.27 (6468 hom., cov: 32)
• Consequence: ENST00000650377.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150

Genes affected

(HGNC:):

SRPRB (HGNC:24085): (SRP receptor subunit beta) The protein encoded by this gene has similarity to mouse protein which is a subunit of the signal recognition particle receptor (SR). This subunit is a transmembrane GTPase belonging to the GTPase superfamily. It anchors alpha subunit, a peripheral membrane GTPase, to the ER membrane. SR is required for the cotranslational targeting of both secretory and membrane proteins to the ER membrane. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105374116	XR_924513.3	n.397-4203G>A		intron_variant, non_coding_transcript_variant
SRPRB	NM_021203.4	c.-173-6057C>T		intron_variant			NP_067026.3
LOC105374116	XR_007096109.1	n.397-4203G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000650377.1	n.3122G>A		non_coding_transcript_exon_variant	2/2
SRPRB	ENST00000466490.7	c.-173-6057C>T		intron_variant		5		ENSP00000418401	P1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41014 AN: 151756 Hom.: 6460 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.270 AC: 41039 AN: 151874 Hom.: 6468 Cov.: 32 AF XY: 0.275 AC XY: 20391 AN XY: 74210

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.462

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.279

Alfa AF: 0.313 Hom.: 3986

Bravo AF: 0.271

Asia WGS AF: 0.385 AC: 1337 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.7
DANN	Benign	0.63

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: rs6794945; hg19: chr3-133518463;