2-45511404-T-C

Position:

• chr2-45511404-T-C

Variant summary

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

The NM_018079.5(SRBD1):​c.1875-23073A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0681 in 152,230 control chromosomes in the GnomAD database, including 559 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 0.068 (559 hom., cov: 32)
• Consequence: SRBD1 NM_018079.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRBD1	NM_018079.5	c.1875-23073A>G		intron_variant		ENST00000263736.5	NP_060549.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRBD1	ENST00000263736.5	c.1875-23073A>G		intron_variant		2	NM_018079.5	ENSP00000263736	P1
SRBD1	ENST00000475073.5	n.282-23073A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0682 AC: 10371 AN: 152112 Hom.: 558 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.0494

Gnomad ASJ AF: 0.0372

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0314

Gnomad FIN AF: 0.0639

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0324

Gnomad OTH AF: 0.0723

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

GnomAD4 genome AF: 0.0681 AC: 10372 AN: 152230 Hom.: 559 Cov.: 32 AF XY: 0.0689 AC XY: 5125 AN XY: 74430

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.0494

Gnomad4 ASJ AF: 0.0372

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0308

Gnomad4 FIN AF: 0.0639

Gnomad4 NFE AF: 0.0324

Gnomad4 OTH AF: 0.0716

Alfa AF: 0.0598 Hom.: 71

Bravo AF: 0.0702

Asia WGS AF: 0.0200 AC: 69 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	0.20
DANN	Benign	0.76

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: rs10490346; hg19: chr2-45738543;