rs3213787

Positions:

• chr2-45419685-A-G

Variant summary

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

The NM_018079.5(SRBD1):​c.2156+103T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0535 in 925,800 control chromosomes in the GnomAD database, including 2,284 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 0.045 (290 hom., cov: 32)
  • Exomes 𝑓: 0.055 (1994 hom.)
• Consequence: SRBD1 NM_018079.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.79

Genes affected

SRBD1 (HGNC:25521): (S1 RNA binding domain 1) Predicted to enable mRNA binding activity. Predicted to be a structural constituent of ribosome. Predicted to be involved in translation. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRBD1	NM_018079.5	c.2156+103T>C		intron_variant		ENST00000263736.5
SRBD1	XM_011532946.3	c.2108+103T>C		intron_variant
SRBD1	XM_047444861.1	c.713+103T>C		intron_variant
SRBD1	XM_047444862.1	c.713+103T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRBD1	ENST00000263736.5	c.2156+103T>C		intron_variant		2	NM_018079.5	P1
SRBD1	ENST00000475073.5	n.480+103T>C		intron_variant, non_coding_transcript_variant		4
SRBD1	ENST00000490133.5	n.1053+103T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0447 AC: 6807 AN: 152176 Hom.: 288 Cov.: 32

Gnomad AFR AF: 0.0147

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0668

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0341

Gnomad OTH AF: 0.0560

GnomAD4 exome AF: 0.0552 AC: 42679 AN: 773506 Hom.: 1994 AF XY: 0.0551 AC XY: 22503 AN XY: 408426

Gnomad4 AFR exome AF: 0.0130

Gnomad4 AMR exome AF: 0.185

Gnomad4 ASJ exome AF: 0.0180

Gnomad4 EAS exome AF: 0.132

Gnomad4 SAS exome AF: 0.0972

Gnomad4 FIN exome AF: 0.0740

Gnomad4 NFE exome AF: 0.0356

Gnomad4 OTH exome AF: 0.0511

GnomAD4 genome AF: 0.0448 AC: 6818 AN: 152294 Hom.: 290 Cov.: 32 AF XY: 0.0477 AC XY: 3550 AN XY: 74460

Gnomad4 AFR AF: 0.0148

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.0167

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.0668

Gnomad4 NFE AF: 0.0341

Gnomad4 OTH AF: 0.0554

Alfa AF: 0.0417 Hom.: 273

Bravo AF: 0.0483

Asia WGS AF: 0.108 AC: 377 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.8
DANN	Benign	0.50

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: rs3213787; hg19: chr2-45646824; COSMIC: COSV55397094;