4-99254913-T-C

Variant names:

• chr4-99254913-T-C
• rs1497379
• ENST00000500358.6:n.3790-31882T>C

Variant summary

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

The ENST00000500358.6(ENSG00000246090):​n.3790-31882T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,040 control chromosomes in the GnomAD database, including 7,165 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 0.28 (7165 hom., cov: 32)
• Consequence: ENSG00000246090 ENST00000500358.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.157
• Publications: 1 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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC100507053	NR_037884.1	n.3790-31882T>C		intron_variant	Intron 4 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000246090	ENST00000500358.6	n.3790-31882T>C		intron_variant	Intron 4 of 9	1
ENSG00000246090	ENST00000509295.5	n.135+850T>C		intron_variant	Intron 1 of 5	1
ENSG00000246090	ENST00000506160.1	n.408-23540T>C		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42999 AN: 151922 Hom.: 7169 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.0240

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.283 AC: 43006 AN: 152040 Hom.: 7165 Cov.: 32 AF XY: 0.276 AC XY: 20490 AN XY: 74300

African (AFR) AF: 0.132 AC: 5476 AN: 41502

American (AMR) AF: 0.264 AC: 4027 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1602 AN: 3468

East Asian (EAS) AF: 0.0241 AC: 125 AN: 5186

South Asian (SAS) AF: 0.156 AC: 751 AN: 4822

European-Finnish (FIN) AF: 0.347 AC: 3668 AN: 10560

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.384 AC: 26118 AN: 67938

Other (OTH) AF: 0.335 AC: 707 AN: 2112

Alfa AF: 0.315 Hom.: 1065

Bravo AF: 0.270

Asia WGS AF: 0.0990 AC: 348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.48
PhyloP100		-0.16

Splicing

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

Other links and lift over

dbSNP: rs1497379; hg19: chr4-100176070;