chr4-148649528-T-C

Variant names:

• chr4-148649528-T-C
• rs2358462
• ENST00000661928.1:n.222+104944T>C

Variant summary

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

The ENST00000661928.1(ENSG00000287292):​n.222+104944T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 152,038 control chromosomes in the GnomAD database, including 10,552 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 0.36 (10552 hom., cov: 32)
• Consequence: ENSG00000287292 ENST00000661928.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.331
• Publications: 8 publications found

Genes affected

ENSG00000287292 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC107986195	XR_001741441.2	n.3661+104944T>C		intron_variant	Intron 2 of 3
LOC105377483	XR_007058326.1	n.319-30727A>G		intron_variant	Intron 1 of 3
LOC105377483	XR_939336.4	n.319-30660A>G		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000287292	ENST00000661928.1	n.222+104944T>C		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54779 AN: 151918 Hom.: 10546 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.360 AC: 54806 AN: 152038 Hom.: 10552 Cov.: 32 AF XY: 0.355 AC XY: 26360 AN XY: 74306

African (AFR) AF: 0.252 AC: 10449 AN: 41470

American (AMR) AF: 0.282 AC: 4307 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1250 AN: 3464

East Asian (EAS) AF: 0.245 AC: 1270 AN: 5184

South Asian (SAS) AF: 0.312 AC: 1499 AN: 4808

European-Finnish (FIN) AF: 0.371 AC: 3923 AN: 10566

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30834 AN: 67960

Other (OTH) AF: 0.356 AC: 748 AN: 2104

Alfa AF: 0.413 Hom.: 31052

Bravo AF: 0.347

Asia WGS AF: 0.292 AC: 1013 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	11
DANN	Benign	0.90
PhyloP100		0.33

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2358462; hg19: chr4-149570680;