2-45466403-A-G

Variant names:

• chr2-45466403-A-G
• rs7603983
• NM_018079.5:c.2049+10590T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_018079.5(SRBD1):​c.2049+10590T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0214 in 151,550 control chromosomes in the GnomAD database, including 34 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 0.021 (34 hom., cov: 32)
• Consequence: SRBD1 NM_018079.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.376
• Publications: 0 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=-0.87).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0214 (3244/151550) while in subpopulation AMR AF = 0.0256 (389/15220). AF 95% confidence interval is 0.0235. There are 34 homozygotes in GnomAd4. There are 1618 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 34 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRBD1	NM_018079.5	c.2049+10590T>C		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.2049+10590T>C		intron_variant	Intron 16 of 20	2	NM_018079.5	ENSP00000263736.4
SRBD1	ENST00000475073.5	n.373+21837T>C		intron_variant	Intron 4 of 5	4

Frequencies

GnomAD3 genomes AF: 0.0214 AC: 3245 AN: 151430 Hom.: 34 Cov.: 32

Gnomad AFR AF: 0.0172

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0255

Gnomad ASJ AF: 0.0294

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.0363

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.0227

Gnomad OTH AF: 0.0361

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

GnomAD4 genome AF: 0.0214 AC: 3244 AN: 151550 Hom.: 34 Cov.: 32 AF XY: 0.0219 AC XY: 1618 AN XY: 74022

African (AFR) AF: 0.0171 AC: 705 AN: 41264

American (AMR) AF: 0.0256 AC: 389 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.0294 AC: 102 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5138

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4796

European-Finnish (FIN) AF: 0.0363 AC: 381 AN: 10498

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0227 AC: 1538 AN: 67866

Other (OTH) AF: 0.0357 AC: 75 AN: 2098

Alfa AF: 0.0218 Hom.: 17

Bravo AF: 0.0214

Asia WGS AF: 0.00404 AC: 14 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.6
DANN	Benign	0.80
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism

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: rs7603983; hg19: chr2-45693542;