rs10503657

Variant names:

• chr8-19184809-G-A
• rs10503657
• ENST00000517949.5:n.535+42359C>T

Variant summary

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

The ENST00000517949.5(ENSG00000253557):​n.535+42359C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,184 control chromosomes in the GnomAD database, including 3,090 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 0.19 (3090 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: ENSG00000253557 ENST00000517949.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.749
• Publications: 2 publications found

Genes affected

ENSG00000253557 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC100128993	NR_038919.1	n.569-147C>T		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000253557	ENST00000517949.5	n.535+42359C>T		intron_variant	Intron 3 of 3	3
ENSG00000253557	ENST00000518417.1	n.279-147C>T		intron_variant	Intron 2 of 3	4
ENSG00000253557	ENST00000520920.5	n.474+42359C>T		intron_variant	Intron 4 of 4	4

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28548 AN: 152062 Hom.: 3079 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.0785

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.188 AC: 28594 AN: 152180 Hom.: 3090 Cov.: 32 AF XY: 0.187 AC XY: 13886 AN XY: 74410

African (AFR) AF: 0.248 AC: 10280 AN: 41500

American (AMR) AF: 0.287 AC: 4389 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 600 AN: 3470

East Asian (EAS) AF: 0.150 AC: 775 AN: 5182

South Asian (SAS) AF: 0.256 AC: 1238 AN: 4830

European-Finnish (FIN) AF: 0.0785 AC: 832 AN: 10598

Middle Eastern (MID) AF: 0.158 AC: 46 AN: 292

European-Non Finnish (NFE) AF: 0.146 AC: 9903 AN: 68002

Other (OTH) AF: 0.183 AC: 387 AN: 2114

Alfa AF: 0.160 Hom.: 1066

Bravo AF: 0.206

Asia WGS AF: 0.194 AC: 673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.67
DANN	Benign	0.61
PhyloP100		-0.75

Splicing

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

Other links and lift over

dbSNP: rs10503657; hg19: chr8-19042319;