rs12459138

Variant names:

• chr19-35357437-G-A
• rs12459138
• ENST00000716259.1:n.771-9815C>T

Variant summary

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

The ENST00000716259.1(ENSG00000288731):​n.771-9815C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,196 control chromosomes in the GnomAD database, including 2,605 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 0.16 (2605 hom., cov: 32)
• Consequence: ENSG00000288731 ENST00000716259.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.708
• Publications: 5 publications found

Genes affected

ENSG00000288731 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000288731	ENST00000716259.1	n.771-9815C>T		intron_variant	Intron 2 of 2
ENSG00000288731	ENST00000786314.1	n.648-9815C>T		intron_variant	Intron 2 of 2
ENSG00000288731	ENST00000786315.1	n.160-9815C>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25023 AN: 152078 Hom.: 2601 Cov.: 32

Gnomad AFR AF: 0.0554

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.164 AC: 25035 AN: 152196 Hom.: 2605 Cov.: 32 AF XY: 0.164 AC XY: 12206 AN XY: 74390

African (AFR) AF: 0.0554 AC: 2303 AN: 41542

American (AMR) AF: 0.192 AC: 2944 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 737 AN: 3472

East Asian (EAS) AF: 0.00386 AC: 20 AN: 5182

South Asian (SAS) AF: 0.222 AC: 1070 AN: 4822

European-Finnish (FIN) AF: 0.202 AC: 2137 AN: 10578

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15234 AN: 67992

Other (OTH) AF: 0.179 AC: 378 AN: 2108

Alfa AF: 0.208 Hom.: 6607

Bravo AF: 0.158

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.67
PhyloP100		-0.71

Splicing

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

Other links and lift over

dbSNP: rs12459138; hg19: chr19-35848339;