rs2251517

Variant names:

• chr21-29159630-T-G
• rs2251517
• NM_001286620.2:c.133-311T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286620.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K7CL	NM_001286620.2	MANE Select	c.133-311T>G		intron	N/A	NP_001273549.1	P57077-4
	MAP3K7CL	NM_001286634.2		c.433-311T>G		intron	N/A	NP_001273563.1	P57077-1
	MAP3K7CL	NM_001371369.1		c.433-311T>G		intron	N/A	NP_001358298.1	P57077-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K7CL	ENST00000399928.6	TSL:1 MANE Select	c.133-311T>G		intron	N/A	ENSP00000382812.1	P57077-4
	MAP3K7CL	ENST00000341618.8	TSL:1	c.433-311T>G		intron	N/A	ENSP00000343212.4	P57077-1
	MAP3K7CL	ENST00000399947.6	TSL:1	c.433-311T>G		intron	N/A	ENSP00000382828.2	P57077-1

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

African (AFR) AF: 0.351 AC: 14561 AN: 41462

American (AMR) AF: 0.384 AC: 5856 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1594 AN: 3470

East Asian (EAS) AF: 0.254 AC: 1312 AN: 5166

South Asian (SAS) AF: 0.496 AC: 2389 AN: 4816

European-Finnish (FIN) AF: 0.518 AC: 5454 AN: 10538

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.470 AC: 31907 AN: 67920

Other (OTH) AF: 0.421 AC: 891 AN: 2116

Alfa AF: 0.433 Hom.: 5717

Bravo AF: 0.412

Asia WGS AF: 0.380 AC: 1318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.38
PhyloP100		-0.11
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2251517;

hg19: chr21-30531951;