Variant 7-20141094-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_182762.4(MACC1):c.2411G>C(p.Arg804Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 1,611,950 control chromosomes in the GnomAD database, including 278,179 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.55 ( 23897 hom., cov: 32)

Exomes 𝑓: 0.59 ( 254282 hom. )

Consequence

MACC1
NM_182762.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.25

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.40167E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MACC1	NM_182762.4 linkuse as main transcript	c.2411G>C	p.Arg804Thr	missense_variant	7/7	ENST00000400331.10	NP_877439.3	Q6ZN28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MACC1	ENST00000400331.10 linkuse as main transcript	c.2411G>C	p.Arg804Thr	missense_variant	7/7	2	NM_182762.4	ENSP00000383185.3	Q6ZN28
MACC1	ENST00000332878.8 linkuse as main transcript	c.2411G>C	p.Arg804Thr	missense_variant	5/5	1		ENSP00000328410.4	Q6ZN28
MACC1	ENST00000589011.1 linkuse as main transcript	c.2411G>C	p.Arg804Thr	missense_variant	5/5	5		ENSP00000466864.1	Q6ZN28

Frequencies

GnomAD3 genomes

AF:

0.550

AC:

83566

AN:

151858

Hom.:

23871

Cov.:

show subpopulations

Gnomad AFR

AF:

0.409

Gnomad AMI

AF:

0.595

Gnomad AMR

AF:

0.615

Gnomad ASJ

AF:

0.632

Gnomad EAS

AF:

0.838

Gnomad SAS

AF:

0.670

Gnomad FIN

AF:

0.598

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.578

Gnomad OTH

AF:

0.596

GnomAD3 exomes

AF:

0.608

AC:

152075

AN:

250314

Hom.:

47449

AF XY:

0.611

AC XY:

82668

AN XY:

135340

show subpopulations

Gnomad AFR exome

AF:

0.406

Gnomad AMR exome

AF:

0.632

Gnomad ASJ exome

AF:

0.632

Gnomad EAS exome

AF:

0.844

Gnomad SAS exome

AF:

0.656

Gnomad FIN exome

AF:

0.592

Gnomad NFE exome

AF:

0.580

Gnomad OTH exome

AF:

0.586

GnomAD4 exome

AF:

0.586

AC:

855796

AN:

1459974

Hom.:

254282

Cov.:

AF XY:

0.589

AC XY:

427963

AN XY:

726334

show subpopulations

Gnomad4 AFR exome

AF:

0.410

Gnomad4 AMR exome

AF:

0.627

Gnomad4 ASJ exome

AF:

0.629

Gnomad4 EAS exome

AF:

0.853

Gnomad4 SAS exome

AF:

0.657

Gnomad4 FIN exome

AF:

0.585

Gnomad4 NFE exome

AF:

0.574

Gnomad4 OTH exome

AF:

0.586

GnomAD4 genome

AF:

0.550

AC:

83631

AN:

151976

Hom.:

23897

Cov.:

AF XY:

0.556

AC XY:

41299

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.409

Gnomad4 AMR

AF:

0.616

Gnomad4 ASJ

AF:

0.632

Gnomad4 EAS

AF:

0.838

Gnomad4 SAS

AF:

0.671

Gnomad4 FIN

AF:

0.598

Gnomad4 NFE

AF:

0.578

Gnomad4 OTH

AF:

0.602

Alfa

AF:

0.582

Hom.:

19625

Bravo

AF:

0.542

TwinsUK

AF:

0.563

AC:

2086

ALSPAC

AF:

0.582

AC:

2242

ESP6500AA

AF:

0.411

AC:

1811

ESP6500EA

AF:

0.582

AC:

5002

ExAC

AF:

0.603

AC:

73249

Asia WGS

AF:

0.730

AC:

2540

AN:

3478

EpiCase

AF:

0.583

EpiControl

AF:

0.583

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

T;T;T

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.82

.;.;T

MetaRNN

Benign

0.0000014

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

M;M;M

PrimateAI

Benign

0.32

PROVEAN

Pathogenic

-4.4

D;D;.

REVEL

Benign

0.19

Sift

Uncertain

0.013

D;D;.

Sift4G

Uncertain

0.0050

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.40

MPC

0.047

ClinPred

0.017

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.32

gMVP

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over