rs6585436

Variant names:

• chr10-117450864-T-C
• rs6585436
• ENST00000549104.1:n.268+14540T>C

Variant summary

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

The ENST00000549104.1(ENSG00000258114):​n.268+14540T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0428 in 152,324 control chromosomes in the GnomAD database, including 194 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 0.043 (194 hom., cov: 33)
• Consequence: ENSG00000258114 ENST00000549104.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.523
• Publications: 9 publications found

Genes affected

ENSG00000258114 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105378502	XR_946344.1	n.95-4189T>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000258114	ENST00000549104.1	n.268+14540T>C		intron_variant	Intron 2 of 2	4
ENSG00000258114	ENST00000821096.1	n.270-4189T>C		intron_variant	Intron 2 of 3
ENSG00000258114	ENST00000821097.1	n.273-4535T>C		intron_variant	Intron 2 of 2
ENSG00000306800	ENST00000821197.1	n.201-872A>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0428 AC: 6515 AN: 152206 Hom.: 193 Cov.: 33

Gnomad AFR AF: 0.0687

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0338

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.0870

Gnomad SAS AF: 0.0561

Gnomad FIN AF: 0.00913

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0257

Gnomad OTH AF: 0.0445

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

GnomAD4 genome AF: 0.0428 AC: 6519 AN: 152324 Hom.: 194 Cov.: 33 AF XY: 0.0422 AC XY: 3145 AN XY: 74480

African (AFR) AF: 0.0687 AC: 2854 AN: 41556

American (AMR) AF: 0.0337 AC: 516 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 417 AN: 3470

East Asian (EAS) AF: 0.0864 AC: 448 AN: 5186

South Asian (SAS) AF: 0.0559 AC: 270 AN: 4828

European-Finnish (FIN) AF: 0.00913 AC: 97 AN: 10620

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0257 AC: 1750 AN: 68042

Other (OTH) AF: 0.0449 AC: 95 AN: 2114

Alfa AF: 0.0353 Hom.: 438

Bravo AF: 0.0457

Asia WGS AF: 0.0780 AC: 272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.1
DANN	Benign	0.61
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs6585436; hg19: chr10-119210375;