Genetic Variant MACC1:c.2347-1273C>T (chr7-20142431-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_182762.4(MACC1):c.2347-1273C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0998 in 152,192 control chromosomes in the GnomAD database, including 918 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 0.10 ( 918 hom., cov: 32)

Consequence

MACC1
NM_182762.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.278

Publications

2 publications found

Variant links:

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 links:

MACC1-AS1 (HGNC:41257): (MACC1 antisense RNA 1)

MACC1-AS1 links:

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new If you want to explore the variant's impact on the transcript NM_182762.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.156 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACC1	NM_182762.4	MANE Select	c.2347-1273C>T		intron	N/A	NP_877439.3
	MACC1-AS1	NR_046756.1		n.105+411G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MACC1	ENST00000400331.10	TSL:2 MANE Select	c.2347-1273C>T	intron	N/A	ENSP00000383185.3	Q6ZN28
MACC1	ENST00000332878.8	TSL:1	c.2347-1273C>T	intron	N/A	ENSP00000328410.4	Q6ZN28
MACC1	ENST00000589011.1	TSL:5	c.2347-1273C>T	intron	N/A	ENSP00000466864.1	Q6ZN28

Frequencies

GnomAD3 genomes

AF:

0.0998

AC:

15179

AN:

152074

Hom.:

917

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0376

Gnomad AMI

AF:

0.158

Gnomad AMR

AF:

0.161

Gnomad ASJ

AF:

0.140

Gnomad EAS

AF:

0.0273

Gnomad SAS

AF:

0.104

Gnomad FIN

AF:

0.0630

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.130

Gnomad OTH

AF:

0.143

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

GnomAD4 genome

AF:

0.0998

AC:

15196

AN:

152192

Hom.:

918

Cov.:

AF XY:

0.0979

AC XY:

7283

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0377

AC:

1565

AN:

41536

American (AMR)

AF:

0.161

AC:

2466

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.140

AC:

487

AN:

3470

East Asian (EAS)

AF:

0.0272

AC:

141

AN:

5184

South Asian (SAS)

AF:

0.105

AC:

504

AN:

4820

European-Finnish (FIN)

AF:

0.0630

AC:

668

AN:

10598

Middle Eastern (MID)

AF:

0.170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.130

AC:

8870

AN:

67986

Other (OTH)

AF:

0.142

AC:

301

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

697

1394

2090

2787

3484

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

352

528

704

880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0988

Hom.:

117

Bravo

AF:

0.105

Asia WGS

AF:

0.0680

AC:

237

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.5

(source)

DANN

Benign

0.70

PhyloP100

0.28

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over