chr21-29160116-G-A

Variant names:

• chr21-29160116-G-A
• rs2832224
• NM_001286620.2:c.248+60G>A

Variant summary

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

The NM_001286620.2(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 NM_001286620.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.912
• Publications: 7 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=-0.89).
• 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 rank	MANE	Protein	UniProt
MAP3K7CL	NM_001286620.2	c.248+60G>A		intron_variant	Intron 4 of 4	ENST00000399928.6	NP_001273549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K7CL	ENST00000399928.6	c.248+60G>A		intron_variant	Intron 4 of 4	1	NM_001286620.2	ENSP00000382812.1

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

African (AFR) AF: 0.200 AC: 5640 AN: 28194

American (AMR) AF: 0.366 AC: 14878 AN: 40658

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 5363 AN: 23356

East Asian (EAS) AF: 0.648 AC: 24563 AN: 37904

South Asian (SAS) AF: 0.275 AC: 21407 AN: 77756

European-Finnish (FIN) AF: 0.274 AC: 14301 AN: 52278

Middle Eastern (MID) AF: 0.198 AC: 1030 AN: 5194

European-Non Finnish (NFE) AF: 0.226 AC: 199813 AN: 884196

Other (OTH) AF: 0.245 AC: 12677 AN: 51730

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

African (AFR) AF: 0.199 AC: 8242 AN: 41508

American (AMR) AF: 0.322 AC: 4917 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 757 AN: 3466

East Asian (EAS) AF: 0.596 AC: 3075 AN: 5156

South Asian (SAS) AF: 0.292 AC: 1407 AN: 4816

European-Finnish (FIN) AF: 0.288 AC: 3048 AN: 10570

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15596 AN: 67978

Other (OTH) AF: 0.246 AC: 520 AN: 2112

Alfa AF: 0.229 Hom.: 5320

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
PhyloP100		-0.91
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: rs2832224; hg19: chr21-30532437;