chr17-19378515-T-C

Variant names:

• chr17-19378515-T-C
• rs2233072
• NM_002749.4:c.-121T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002749.4(MAPK7):​c.-121T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000106 in 943,124 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: MAPK7 NM_002749.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202
• Publications: 0 publications found

Genes affected

MAPK7 (HGNC:6880): (mitogen-activated protein kinase 7) The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is specifically activated by mitogen-activated protein kinase kinase 5 (MAP2K5/MEK5). It is involved in the downstream signaling processes of various receptor molecules including receptor type kinases, and G protein-coupled receptors. In response to extracelluar signals, this kinase translocates to cell nucleus, where it regulates gene expression by phosphorylating, and activating different transcription factors. Four alternatively spliced transcript variants of this gene encoding two distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002749.4. 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
	MAPK7	NM_002749.4	MANE Select	c.-121T>C		5_prime_UTR	Exon 1 of 7	NP_002740.2
	MAPK7	NM_139034.3		c.-33T>C		5_prime_UTR	Exon 1 of 7	NP_620603.2	Q13164-1
	MAPK7	NM_139033.3		c.-5-381T>C		intron	N/A	NP_620602.2	Q13164-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK7	ENST00000395604.8	TSL:1 MANE Select	c.-121T>C		5_prime_UTR	Exon 1 of 7	ENSP00000378968.3	Q13164-1
	MAPK7	ENST00000395602.8	TSL:1	c.-33T>C		5_prime_UTR	Exon 1 of 7	ENSP00000378966.4	Q13164-1
	MAPK7	ENST00000308406.9	TSL:1	c.-5-381T>C		intron	N/A	ENSP00000311005.5	Q13164-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000106 AC: 1 AN: 943124 Hom.: 0 Cov.: 44 AF XY: 0.00000225 AC XY: 1 AN XY: 443726

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 18316

American (AMR) AF: 0.00 AC: 0 AN: 5360

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8248

East Asian (EAS) AF: 0.00 AC: 0 AN: 8682

South Asian (SAS) AF: 0.00 AC: 0 AN: 33848

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5886

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2100

European-Non Finnish (NFE) AF: 0.00000121 AC: 1 AN: 827090

Other (OTH) AF: 0.00 AC: 0 AN: 33594

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.0
DANN	Benign	0.63
PhyloP100		0.20
PromoterAI		0.045	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2233072; hg19: chr17-19281828;