rs1999321

Variant names:

• chr21-29157912-A-C
• rs1999321
• NM_001286620.2:c.133-2029A>C

Variant summary

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

The NM_001286620.2(MAP3K7CL):​c.133-2029A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 152,052 control chromosomes in the GnomAD database, including 24,333 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 0.56 (24333 hom., cov: 32)
• Consequence: MAP3K7CL NM_001286620.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102
• Publications: 9 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.644 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K7CL	NM_001286620.2	MANE Select	c.133-2029A>C		intron	N/A	NP_001273549.1
	MAP3K7CL	NM_001286634.2		c.433-2029A>C		intron	N/A	NP_001273563.1
	MAP3K7CL	NM_001371369.1		c.433-2029A>C		intron	N/A	NP_001358298.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K7CL	ENST00000399928.6	TSL:1 MANE Select	c.133-2029A>C		intron	N/A	ENSP00000382812.1
	MAP3K7CL	ENST00000341618.8	TSL:1	c.433-2029A>C		intron	N/A	ENSP00000343212.4
	MAP3K7CL	ENST00000399947.6	TSL:1	c.433-2029A>C		intron	N/A	ENSP00000382828.2

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85327 AN: 151934 Hom.: 24300 Cov.: 32

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.537

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

GnomAD4 genome AF: 0.562 AC: 85411 AN: 152052 Hom.: 24333 Cov.: 32 AF XY: 0.562 AC XY: 41758 AN XY: 74330

African (AFR) AF: 0.651 AC: 26969 AN: 41448

American (AMR) AF: 0.524 AC: 8008 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.568 AC: 1971 AN: 3472

East Asian (EAS) AF: 0.399 AC: 2063 AN: 5172

South Asian (SAS) AF: 0.616 AC: 2973 AN: 4828

European-Finnish (FIN) AF: 0.544 AC: 5750 AN: 10568

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.526 AC: 35739 AN: 67970

Other (OTH) AF: 0.538 AC: 1138 AN: 2114

Alfa AF: 0.538 Hom.: 60899

Bravo AF: 0.563

Asia WGS AF: 0.522 AC: 1812 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.8
DANN	Benign	0.41
PhyloP100		0.10
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: rs1999321; hg19: chr21-30530233;