4-99103732-A-G

Variant names:

• chr4-99103732-A-G
• rs2851275
• ENST00000500358.6:n.428+14448A>G

Variant summary

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

The ENST00000500358.6(ENSG00000246090):​n.428+14448A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,092 control chromosomes in the GnomAD database, including 10,342 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 0.34 (10342 hom., cov: 32)
• Consequence: ENSG00000246090 ENST00000500358.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.506
• Publications: 5 publications found

Genes affected

ENSG00000246090 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC100507053	NR_037884.1	n.428+14448A>G		intron_variant	Intron 1 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000246090	ENST00000500358.6	n.428+14448A>G		intron_variant	Intron 1 of 9	1
ENSG00000246090	ENST00000661393.1	n.425+14448A>G		intron_variant	Intron 1 of 9
ENSG00000246090	ENST00000670724.2	n.480+14448A>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51391 AN: 151974 Hom.: 10337 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.350

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

GnomAD4 genome AF: 0.338 AC: 51395 AN: 152092 Hom.: 10342 Cov.: 32 AF XY: 0.341 AC XY: 25359 AN XY: 74356

African (AFR) AF: 0.134 AC: 5564 AN: 41544

American (AMR) AF: 0.329 AC: 5029 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1354 AN: 3470

East Asian (EAS) AF: 0.129 AC: 670 AN: 5180

South Asian (SAS) AF: 0.511 AC: 2461 AN: 4820

European-Finnish (FIN) AF: 0.453 AC: 4781 AN: 10556

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30301 AN: 67936

Other (OTH) AF: 0.353 AC: 745 AN: 2110

Alfa AF: 0.337 Hom.: 3728

Bravo AF: 0.313

Asia WGS AF: 0.374 AC: 1302 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.7
DANN	Benign	0.70
PhyloP100		-0.51

Splicing

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

Other links and lift over

dbSNP: rs2851275; hg19: chr4-100024883;