chr21-29086433-T-C

Variant names:

• chr21-29086433-T-C
• rs8133819
• ENST00000341618.8:c.57+516T>C

Variant summary

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

The ENST00000341618.8(MAP3K7CL):​c.57+516T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,090 control chromosomes in the GnomAD database, including 2,648 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 0.18 (2648 hom., cov: 32)
• Consequence: MAP3K7CL ENST00000341618.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540
• Publications: 14 publications found

Genes affected

MAP3K7CL (HGNC:16457): (MAP3K7 C-terminal like) Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000341618.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K7CL	NM_001286634.2		c.57+516T>C		intron	N/A	NP_001273563.1
	MAP3K7CL	NM_001371369.1		c.57+516T>C		intron	N/A	NP_001358298.1
	MAP3K7CL	NM_020152.4		c.57+516T>C		intron	N/A	NP_064537.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K7CL	ENST00000341618.8	TSL:1	c.57+516T>C		intron	N/A	ENSP00000343212.4
	MAP3K7CL	ENST00000399947.6	TSL:1	c.57+516T>C		intron	N/A	ENSP00000382828.2
	MAP3K7CL	ENST00000496779.5	TSL:1	n.505+516T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26738 AN: 151972 Hom.: 2645 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.0429

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0886

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.176 AC: 26758 AN: 152090 Hom.: 2648 Cov.: 32 AF XY: 0.171 AC XY: 12723 AN XY: 74362

African (AFR) AF: 0.270 AC: 11194 AN: 41460

American (AMR) AF: 0.180 AC: 2742 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 632 AN: 3472

East Asian (EAS) AF: 0.146 AC: 756 AN: 5188

South Asian (SAS) AF: 0.123 AC: 594 AN: 4818

European-Finnish (FIN) AF: 0.0886 AC: 938 AN: 10588

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9429 AN: 67982

Other (OTH) AF: 0.182 AC: 383 AN: 2110

Alfa AF: 0.151 Hom.: 8171

Bravo AF: 0.187

Asia WGS AF: 0.154 AC: 536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.7
DANN	Benign	0.72
PhyloP100		-0.054
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs8133819; hg19: chr21-30458754;