rs9978281

chr21-29081883-T-C

Variant summary

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

The ENST00000341618.8(MAP3K7CL):c.-48-3930T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.859 in 152,200 control chromosomes in the GnomAD database, including 56,450 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 0.86 (56450 hom., cov: 31)
• Consequence: MAP3K7CL ENST00000341618.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP3K7CL	NM_001286617.2	c.-586-3930T>C		intron_variant
MAP3K7CL	NM_001286618.2	c.-457-3930T>C		intron_variant
MAP3K7CL	NM_001286622.2	c.-510-3930T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP3K7CL	ENST00000341618.8	c.-48-3930T>C		intron_variant		1
MAP3K7CL	ENST00000399947.6	c.-121+1175T>C		intron_variant		1
MAP3K7CL	ENST00000496779.5	n.400+1175T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.859 AC: 130585 AN: 152082 Hom.: 56389 Cov.: 31

Gnomad AFR AF: 0.937

Gnomad AMI AF: 0.853

Gnomad AMR AF: 0.778

Gnomad ASJ AF: 0.848

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.888

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.839

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

GnomAD4 genome AF: 0.859 AC: 130709 AN: 152200 Hom.: 56450 Cov.: 31 AF XY: 0.858 AC XY: 63854 AN XY: 74420

Gnomad4 AFR AF: 0.937

Gnomad4 AMR AF: 0.778

Gnomad4 ASJ AF: 0.848

Gnomad4 EAS AF: 0.638

Gnomad4 SAS AF: 0.888

Gnomad4 FIN AF: 0.888

Gnomad4 NFE AF: 0.841

Gnomad4 OTH AF: 0.839

Alfa AF: 0.870 Hom.: 8259

Bravo AF: 0.851

Asia WGS AF: 0.787 AC: 2739 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.82
Dann	Benign	0.28

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: rs9978281; hg19: chr21-30454204;