21-29160116-G-A

Position:

• chr21-29160116-G-A

Variant summary

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

The ENST00000399928.6(MAP3K7CL):​c.248+60G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 1,353,344 control chromosomes in the GnomAD database, including 46,815 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 0.25 (5157 hom., cov: 33)
  • Exomes 𝑓: 0.25 (41658 hom.)
• Consequence: MAP3K7CL ENST00000399928.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.912

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K7CL	NM_001286620.2	c.248+60G>A		intron_variant		ENST00000399928.6	NP_001273549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K7CL	ENST00000399928.6	c.248+60G>A		intron_variant		1	NM_001286620.2	ENSP00000382812	P1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37749 AN: 151960 Hom.: 5151 Cov.: 33

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.245

GnomAD4 exome AF: 0.249 AC: 299672 AN: 1201266 Hom.: 41658 AF XY: 0.250 AC XY: 152100 AN XY: 607630

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.366

Gnomad4 ASJ exome AF: 0.230

Gnomad4 EAS exome AF: 0.648

Gnomad4 SAS exome AF: 0.275

Gnomad4 FIN exome AF: 0.274

Gnomad4 NFE exome AF: 0.226

Gnomad4 OTH exome AF: 0.245

GnomAD4 genome AF: 0.248 AC: 37782 AN: 152078 Hom.: 5157 Cov.: 33 AF XY: 0.256 AC XY: 19009 AN XY: 74342

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.596

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.246

Alfa AF: 0.226 Hom.: 3975

Bravo AF: 0.251

Asia WGS AF: 0.412 AC: 1433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.42

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: rs2832224; hg19: chr21-30532437;