7-20176725-C-T

Position:

• chr7-20176725-C-T

Variant summary

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

The NM_182762.4(MACC1):​c.-217-5947G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 151,988 control chromosomes in the GnomAD database, including 19,611 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 0.48 (19611 hom., cov: 33)
• Consequence: MACC1 NM_182762.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122

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]

MACC1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MACC1	NM_182762.4	c.-217-5947G>A		intron_variant		ENST00000400331.10	NP_877439.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MACC1	ENST00000400331.10	c.-217-5947G>A		intron_variant		2	NM_182762.4	ENSP00000383185.3

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73588 AN: 151870 Hom.: 19570 Cov.: 33

Gnomad AFR AF: 0.660

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.472

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

GnomAD4 genome AF: 0.485 AC: 73695 AN: 151988 Hom.: 19611 Cov.: 33 AF XY: 0.490 AC XY: 36391 AN XY: 74306

Gnomad4 AFR AF: 0.660

Gnomad4 AMR AF: 0.530

Gnomad4 ASJ AF: 0.480

Gnomad4 EAS AF: 0.858

Gnomad4 SAS AF: 0.562

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.472

Alfa AF: 0.319 Hom.: 1453

Bravo AF: 0.506

Asia WGS AF: 0.683 AC: 2378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.4
DANN	Benign	0.50

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: rs3114446; hg19: chr7-20216348;