rs2251517

Positions:

• chr21-29159630-T-G

Variant summary

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

The NM_001286620.2(MAP3K7CL):​c.133-311T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 151,942 control chromosomes in the GnomAD database, including 14,149 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 0.43 (14149 hom., cov: 31)
• Consequence: MAP3K7CL NM_001286620.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP3K7CL	NM_001286620.2	c.133-311T>G		intron_variant		ENST00000399928.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP3K7CL	ENST00000399928.6	c.133-311T>G		intron_variant		1	NM_001286620.2	P1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64596 AN: 151824 Hom.: 14132 Cov.: 31

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.426 AC: 64652 AN: 151942 Hom.: 14149 Cov.: 31 AF XY: 0.427 AC XY: 31736 AN XY: 74256

Gnomad4 AFR AF: 0.351

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.459

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.518

Gnomad4 NFE AF: 0.470

Gnomad4 OTH AF: 0.421

Alfa AF: 0.444 Hom.: 3397

Bravo AF: 0.412

Asia WGS AF: 0.380 AC: 1318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs2251517; hg19: chr21-30531951;