4-120553417-A-G

Variant names:

• chr4-120553417-A-G
• rs4833652
• ENST00000653046.1:n.271-10894A>G

Variant summary

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

The ENST00000653046.1(MAD2L1-DT):​n.271-10894A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 151,906 control chromosomes in the GnomAD database, including 10,540 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 0.35 (10540 hom., cov: 31)
• Consequence: MAD2L1-DT ENST00000653046.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190
• Publications: 2 publications found

Genes affected

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.534 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	ENST00000653046.1	n.271-10894A>G		intron_variant	Intron 2 of 2
MAD2L1-DT	ENST00000740075.1	n.78-9003A>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.349 AC: 52967 AN: 151788 Hom.: 10532 Cov.: 31

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.349 AC: 52992 AN: 151906 Hom.: 10540 Cov.: 31 AF XY: 0.341 AC XY: 25295 AN XY: 74258

African (AFR) AF: 0.540 AC: 22377 AN: 41430

American (AMR) AF: 0.266 AC: 4060 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1196 AN: 3468

East Asian (EAS) AF: 0.109 AC: 563 AN: 5156

South Asian (SAS) AF: 0.178 AC: 856 AN: 4810

European-Finnish (FIN) AF: 0.248 AC: 2620 AN: 10558

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20065 AN: 67926

Other (OTH) AF: 0.385 AC: 809 AN: 2104

Alfa AF: 0.315 Hom.: 27605

Bravo AF: 0.361

Asia WGS AF: 0.139 AC: 484 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.0
DANN	Benign	0.34
PhyloP100		-0.19

Splicing

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

Other links and lift over

dbSNP: rs4833652; hg19: chr4-121474572;