2-45441734-G-T

Variant names:

• chr2-45441734-G-T
• rs3770252
• NM_018079.5:c.2050-21840C>A

Variant summary

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

The NM_018079.5(SRBD1):​c.2050-21840C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0277 in 152,296 control chromosomes in the GnomAD database, including 145 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 0.028 (145 hom., cov: 32)
• Consequence: SRBD1 NM_018079.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.719
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRBD1	NM_018079.5	c.2050-21840C>A		intron_variant	Intron 16 of 20	ENST00000263736.5	NP_060549.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRBD1	ENST00000263736.5	c.2050-21840C>A		intron_variant	Intron 16 of 20	2	NM_018079.5	ENSP00000263736.4
SRBD1	ENST00000475073.5	n.374-21840C>A		intron_variant	Intron 4 of 5	4
SRBD1	ENST00000490133.5	n.946+5416C>A		intron_variant	Intron 1 of 5	2

Frequencies

GnomAD3 genomes AF: 0.0277 AC: 4213 AN: 152178 Hom.: 143 Cov.: 32

Gnomad AFR AF: 0.00683

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0884

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.0833

Gnomad SAS AF: 0.0145

Gnomad FIN AF: 0.0356

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0230

Gnomad OTH AF: 0.0201

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

GnomAD4 genome AF: 0.0277 AC: 4218 AN: 152296 Hom.: 145 Cov.: 32 AF XY: 0.0296 AC XY: 2204 AN XY: 74470

African (AFR) AF: 0.00681 AC: 283 AN: 41574

American (AMR) AF: 0.0888 AC: 1357 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0248 AC: 86 AN: 3472

East Asian (EAS) AF: 0.0837 AC: 434 AN: 5184

South Asian (SAS) AF: 0.0141 AC: 68 AN: 4828

European-Finnish (FIN) AF: 0.0356 AC: 378 AN: 10614

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0230 AC: 1567 AN: 68014

Other (OTH) AF: 0.0194 AC: 41 AN: 2114

Alfa AF: 0.0241 Hom.: 31

Bravo AF: 0.0318

Asia WGS AF: 0.0360 AC: 124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.3
DANN	Benign	0.80
PhyloP100		0.72
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: rs3770252; hg19: chr2-45668873;