rs10518429

Variant names:

• chr4-124292344-C-T
• rs10518429
• ENST00000818434.1:n.178-40304G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000818434.1(ENSG00000286734):​n.178-40304G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0249 in 152,118 control chromosomes in the GnomAD database, including 70 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 0.025 (70 hom., cov: 32)
• Consequence: ENSG00000286734 ENST00000818434.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.280
• Publications: 2 publications found

Genes affected

ENSG00000286734 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0249 (3792/152118) while in subpopulation NFE AF = 0.0355 (2415/67982). AF 95% confidence interval is 0.0343. There are 70 homozygotes in GnomAd4. There are 1907 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 70 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105377406	XR_001741813.2	n.2964-15859C>T		intron_variant	Intron 3 of 4
LOC105377406	XR_001741814.2	n.241-15862C>T		intron_variant	Intron 2 of 3
LOC105377406	XR_001741821.2	n.199-15859C>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000286734	ENST00000818434.1	n.178-40304G>A		intron_variant	Intron 1 of 3
ENSG00000286734	ENST00000818435.1	n.169-40304G>A		intron_variant	Intron 1 of 2
ENSG00000286734	ENST00000818436.1	n.109-40304G>A		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0249 AC: 3792 AN: 152000 Hom.: 70 Cov.: 32

Gnomad AFR AF: 0.00638

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0160

Gnomad ASJ AF: 0.0297

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0294

Gnomad FIN AF: 0.0545

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0355

Gnomad OTH AF: 0.0191

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

GnomAD4 genome AF: 0.0249 AC: 3792 AN: 152118 Hom.: 70 Cov.: 32 AF XY: 0.0256 AC XY: 1907 AN XY: 74386

African (AFR) AF: 0.00636 AC: 264 AN: 41528

American (AMR) AF: 0.0160 AC: 244 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0297 AC: 103 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.0299 AC: 144 AN: 4822

European-Finnish (FIN) AF: 0.0545 AC: 575 AN: 10558

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0355 AC: 2415 AN: 67982

Other (OTH) AF: 0.0189 AC: 40 AN: 2112

Alfa AF: 0.0301 Hom.: 21

Bravo AF: 0.0204

Asia WGS AF: 0.00955 AC: 33 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.53
PhyloP100		0.28

Splicing

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

Other links and lift over

dbSNP: rs10518429; hg19: chr4-125213499;