rs10518357

Variant names:

• chr4-120297169-A-T
• rs10518357
• ENST00000504106.5:n.159-31364A>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000504106.5(MAD2L1-DT):​n.159-31364A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0419 in 152,174 control chromosomes in the GnomAD database, including 420 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 0.042 (420 hom., cov: 32)
• Consequence: MAD2L1-DT ENST00000504106.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0460

Genes affected

MAD2L1-DT (HGNC:55546): (MAD2L1 divergent transcript)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 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
MAD2L1-DT	ENST00000504106.5	n.159-31364A>T		intron_variant	Intron 3 of 5	3
MAD2L1-DT	ENST00000508362.1	n.139-31364A>T		intron_variant	Intron 2 of 5	4
MAD2L1-DT	ENST00000653046.1	n.176+34809A>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0418 AC: 6361 AN: 152056 Hom.: 419 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0158

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0334

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00182

Gnomad OTH AF: 0.0306

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

GnomAD4 genome AF: 0.0419 AC: 6370 AN: 152174 Hom.: 420 Cov.: 32 AF XY: 0.0412 AC XY: 3064 AN XY: 74440

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.0158

Gnomad4 ASJ AF: 0.0167

Gnomad4 EAS AF: 0.00213

Gnomad4 SAS AF: 0.0336

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00182

Gnomad4 OTH AF: 0.0303

Alfa AF: 0.0245 Hom.: 29

Bravo AF: 0.0471

Asia WGS AF: 0.0200 AC: 68 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	2.4
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10518357; hg19: chr4-121218324;