chr7-20212017-T-A

Variant names:

• chr7-20212017-T-A
• rs3095009
• NM_182762.4:c.-218+5282A>T

Variant summary

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

The NM_182762.4(MACC1):​c.-218+5282A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: MACC1 NM_182762.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.602
• Publications: 4 publications found

Genes affected

MACC1 (HGNC:30215): (MET transcriptional regulator MACC1) MACC1 is a key regulator of the hepatocyte growth factor (HGF; MIM 142409)-HGF receptor (HGFR, or MET; MIM 164860) pathway, which is involved in cellular growth, epithelial-mesenchymal transition, angiogenesis, cell motility, invasiveness, and metastasis. Expression of MACC1 in colon cancer (MIM 114500) specimens is an independent prognostic indicator for metastasis formation and metastasis-free survival (Stein et al., 2009 [PubMed 19098908]).[supplied by OMIM, Mar 2009]

GIRGL (HGNC:55702): (glutamine insufficiency regulator of glutaminase lncRNA)

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=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182762.4. 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
	MACC1	NM_182762.4	MANE Select	c.-218+5282A>T		intron	N/A	NP_877439.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACC1	ENST00000400331.10	TSL:2 MANE Select	c.-218+5282A>T		intron	N/A	ENSP00000383185.3	Q6ZN28
	MACC1	ENST00000332878.8	TSL:1	c.-9+5282A>T		intron	N/A	ENSP00000328410.4	Q6ZN28
	MACC1	ENST00000910134.1		c.-260+5282A>T		intron	N/A	ENSP00000580193.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.33
DANN	Benign	0.25
PhyloP100		-0.60

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: rs3095009; hg19: chr7-20251640;