4-99254850-A-C

Variant names:

• chr4-99254850-A-C
• rs1230021
• ENST00000500358.6:n.3790-31945A>C

Variant summary

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

The ENST00000500358.6(ENSG00000246090):​n.3790-31945A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.965 in 152,226 control chromosomes in the GnomAD database, including 70,904 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 0.97 (70904 hom., cov: 31)
• Consequence: ENSG00000246090 ENST00000500358.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 0 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC100507053	NR_037884.1	n.3790-31945A>C		intron_variant	Intron 4 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000246090	ENST00000500358.6	n.3790-31945A>C		intron_variant	Intron 4 of 9	1
ENSG00000246090	ENST00000509295.5	n.135+787A>C		intron_variant	Intron 1 of 5	1
ENSG00000246090	ENST00000506160.1	n.408-23603A>C		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.965 AC: 146796 AN: 152108 Hom.: 70849 Cov.: 31

Gnomad AFR AF: 0.959

Gnomad AMI AF: 0.980

Gnomad AMR AF: 0.954

Gnomad ASJ AF: 0.977

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.973

Gnomad FIN AF: 0.944

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.970

Gnomad OTH AF: 0.968

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

GnomAD4 genome AF: 0.965 AC: 146910 AN: 152226 Hom.: 70904 Cov.: 31 AF XY: 0.965 AC XY: 71794 AN XY: 74424

African (AFR) AF: 0.959 AC: 39824 AN: 41534

American (AMR) AF: 0.954 AC: 14576 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.977 AC: 3391 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5167 AN: 5170

South Asian (SAS) AF: 0.973 AC: 4691 AN: 4822

European-Finnish (FIN) AF: 0.944 AC: 10021 AN: 10612

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 0.970 AC: 66010 AN: 68022

Other (OTH) AF: 0.968 AC: 2045 AN: 2112

Alfa AF: 0.965 Hom.: 8935

Bravo AF: 0.963

Asia WGS AF: 0.978 AC: 3403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.47
DANN	Benign	0.44
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs1230021; hg19: chr4-100176007;