rs3213787

Variant names:

• chr2-45419685-A-G
• rs3213787
• NM_018079.5:c.2156+103T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 31 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SRBD1	NM_018079.5	c.2156+103T>C		intron_variant	Intron 17 of 20	ENST00000263736.5	NP_060549.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRBD1	ENST00000263736.5	c.2156+103T>C		intron_variant	Intron 17 of 20	2	NM_018079.5	ENSP00000263736.4
SRBD1	ENST00000475073.5	n.480+103T>C		intron_variant	Intron 5 of 5	4
SRBD1	ENST00000490133.5	n.1053+103T>C		intron_variant	Intron 2 of 5	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

African (AFR) AF: 0.0130 AC: 260 AN: 20070

American (AMR) AF: 0.185 AC: 7569 AN: 40910

Ashkenazi Jewish (ASJ) AF: 0.0180 AC: 374 AN: 20742

East Asian (EAS) AF: 0.132 AC: 4656 AN: 35264

South Asian (SAS) AF: 0.0972 AC: 6657 AN: 68462

European-Finnish (FIN) AF: 0.0740 AC: 3205 AN: 43304

Middle Eastern (MID) AF: 0.0260 AC: 114 AN: 4386

European-Non Finnish (NFE) AF: 0.0356 AC: 17917 AN: 502644

Other (OTH) AF: 0.0511 AC: 1927 AN: 37724

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

African (AFR) AF: 0.0148 AC: 616 AN: 41572

American (AMR) AF: 0.118 AC: 1799 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0167 AC: 58 AN: 3472

East Asian (EAS) AF: 0.129 AC: 671 AN: 5182

South Asian (SAS) AF: 0.109 AC: 523 AN: 4818

European-Finnish (FIN) AF: 0.0668 AC: 709 AN: 10610

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0341 AC: 2318 AN: 68026

Other (OTH) AF: 0.0554 AC: 117 AN: 2112

Alfa AF: 0.0415 Hom.: 684

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
PhyloP100		2.8
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: rs3213787; hg19: chr2-45646824; COSMIC: COSV55397094;