7-20141094-C-G

Variant names:

• chr7-20141094-C-G
• rs3735615
• NM_182762.4:c.2411G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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.

• Frequency:
  • Genomes: 𝑓 0.55 (23897 hom., cov: 32)
  • Exomes 𝑓: 0.59 (254282 hom.)
• Consequence: MACC1 NM_182762.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.25
• Publications: 50 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]

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MACC1	NM_182762.4	c.2411G>C	p.Arg804Thr	missense_variant	Exon 7 of 7	ENST00000400331.10	NP_877439.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACC1	ENST00000400331.10	c.2411G>C	p.Arg804Thr	missense_variant	Exon 7 of 7	2	NM_182762.4	ENSP00000383185.3

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83566 AN: 151858 Hom.: 23871 Cov.: 32

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

GnomAD2 exomes AF: 0.608 AC: 152075 AN: 250314 AF XY: 0.611

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 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.: 39 AF XY: 0.589 AC XY: 427963 AN XY: 726334

African (AFR) AF: 0.410 AC: 13713 AN: 33444

American (AMR) AF: 0.627 AC: 28009 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 16432 AN: 26108

East Asian (EAS) AF: 0.853 AC: 33844 AN: 39672

South Asian (SAS) AF: 0.657 AC: 56559 AN: 86138

European-Finnish (FIN) AF: 0.585 AC: 31041 AN: 53070

Middle Eastern (MID) AF: 0.576 AC: 3320 AN: 5760

European-Non Finnish (NFE) AF: 0.574 AC: 637526 AN: 1110752

Other (OTH) AF: 0.586 AC: 35352 AN: 60352

GnomAD4 genome AF: 0.550 AC: 83631 AN: 151976 Hom.: 23897 Cov.: 32 AF XY: 0.556 AC XY: 41299 AN XY: 74276

African (AFR) AF: 0.409 AC: 16935 AN: 41410

American (AMR) AF: 0.616 AC: 9403 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.632 AC: 2194 AN: 3472

East Asian (EAS) AF: 0.838 AC: 4349 AN: 5192

South Asian (SAS) AF: 0.671 AC: 3227 AN: 4812

European-Finnish (FIN) AF: 0.598 AC: 6300 AN: 10534

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.578 AC: 39259 AN: 67974

Other (OTH) AF: 0.602 AC: 1271 AN: 2112

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	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	22
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	D
LIST_S2	Benign	0.82	.;.;T
MetaRNN	Benign	0.0000014	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M;M;M
PhyloP100		3.3
PrimateAI	Benign	0.32	T
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	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.32
gMVP		0.60
Mutation Taster		=99/1	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: rs3735615; hg19: chr7-20180717; COSMIC: COSV60542176; COSMIC: COSV60542176;