7-20176725-C-T

Variant names:

• chr7-20176725-C-T
• rs3114446
• NM_182762.4:c.-217-5947G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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]

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACC1	NM_182762.4	MANE Select	c.-217-5947G>A		intron	N/A	NP_877439.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACC1	ENST00000400331.10	TSL:2 MANE Select	c.-217-5947G>A		intron	N/A	ENSP00000383185.3
	MACC1	ENST00000332878.8	TSL:1	c.-8-14855G>A		intron	N/A	ENSP00000328410.4
	MACC1	ENST00000589011.1	TSL:5	c.-9+8264G>A		intron	N/A	ENSP00000466864.1

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

African (AFR) AF: 0.660 AC: 27398 AN: 41484

American (AMR) AF: 0.530 AC: 8092 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1665 AN: 3470

East Asian (EAS) AF: 0.858 AC: 4452 AN: 5188

South Asian (SAS) AF: 0.562 AC: 2716 AN: 4832

European-Finnish (FIN) AF: 0.333 AC: 3524 AN: 10568

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.361 AC: 24505 AN: 67852

Other (OTH) AF: 0.472 AC: 994 AN: 2106

Alfa AF: 0.401 Hom.: 4608

Bravo AF: 0.506

Asia WGS AF: 0.683 AC: 2378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.4
DANN	Benign	0.50
PhyloP100		0.12
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: rs3114446; hg19: chr7-20216348;