rs9853615

Positions:

• chr3-133801137-A-G
• chr3-133801137-A-T

Variant summary

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

The ENST00000650377.1(ENSG00000285908):​n.1604T>C 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 0.338 in 152,048 control chromosomes in the GnomAD database, including 8,838 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 0.34 (8838 hom., cov: 32)
• Consequence: ENST00000650377.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.189

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC105374116	XR_924513.3	n.396+3951T>C		intron_variant, non_coding_transcript_variant
SRPRB	NM_021203.4	c.-173-4539A>G		intron_variant
LOC105374116	XR_007096109.1	n.396+3951T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000650377.1	n.1604T>C		non_coding_transcript_exon_variant	2/2
SRPRB	ENST00000466490.7	c.-173-4539A>G		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51393 AN: 151930 Hom.: 8832 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.338 AC: 51420 AN: 152048 Hom.: 8838 Cov.: 32 AF XY: 0.335 AC XY: 24919 AN XY: 74302

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.429

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.339

Alfa AF: 0.362 Hom.: 20725

Bravo AF: 0.332

Asia WGS AF: 0.223 AC: 779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.4
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs9853615; hg19: chr3-133519981;