chr7-20161772-G-C

Variant names:

• chr7-20161772-G-C
• rs4721888
• NM_182762.4:c.91C>G

Variant summary

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

The NM_182762.4(MACC1):​c.91C>G​(p.Leu31Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0848 in 1,609,940 control chromosomes in the GnomAD database, including 7,224 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.069 (561 hom., cov: 33)
  • Exomes 𝑓: 0.086 (6663 hom.)
• Consequence: MACC1 NM_182762.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0620
• Publications: 27 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 (MetaRNN=0.006849557).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACC1	NM_182762.4	c.91C>G	p.Leu31Val	missense_variant	Exon 4 of 7	ENST00000400331.10	NP_877439.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACC1	ENST00000400331.10	c.91C>G	p.Leu31Val	missense_variant	Exon 4 of 7	2	NM_182762.4	ENSP00000383185.3
MACC1	ENST00000332878.8	c.91C>G	p.Leu31Val	missense_variant	Exon 2 of 5	1		ENSP00000328410.4
MACC1	ENST00000589011.1	c.91C>G	p.Leu31Val	missense_variant	Exon 2 of 5	5		ENSP00000466864.1

Frequencies

GnomAD3 genomes AF: 0.0693 AC: 10531 AN: 151868 Hom.: 561 Cov.: 33

Gnomad AFR AF: 0.0182

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0704

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0599

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0798

Gnomad OTH AF: 0.0705

GnomAD2 exomes AF: 0.0949 AC: 23797 AN: 250872 AF XY: 0.0985

Gnomad AFR exome AF: 0.0156

Gnomad AMR exome AF: 0.0601

Gnomad ASJ exome AF: 0.105

Gnomad EAS exome AF: 0.279

Gnomad FIN exome AF: 0.0634

Gnomad NFE exome AF: 0.0807

Gnomad OTH exome AF: 0.0913

GnomAD4 exome AF: 0.0864 AC: 125919 AN: 1457954 Hom.: 6663 Cov.: 30 AF XY: 0.0883 AC XY: 64095 AN XY: 725470

African (AFR) AF: 0.0134 AC: 449 AN: 33402

American (AMR) AF: 0.0621 AC: 2774 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 2752 AN: 26058

East Asian (EAS) AF: 0.249 AC: 9823 AN: 39498

South Asian (SAS) AF: 0.137 AC: 11788 AN: 86102

European-Finnish (FIN) AF: 0.0623 AC: 3324 AN: 53340

Middle Eastern (MID) AF: 0.0970 AC: 558 AN: 5752

European-Non Finnish (NFE) AF: 0.0801 AC: 88851 AN: 1108924

Other (OTH) AF: 0.0930 AC: 5600 AN: 60214

GnomAD4 genome AF: 0.0693 AC: 10528 AN: 151986 Hom.: 561 Cov.: 33 AF XY: 0.0706 AC XY: 5245 AN XY: 74278

African (AFR) AF: 0.0182 AC: 754 AN: 41534

American (AMR) AF: 0.0703 AC: 1073 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 378 AN: 3464

East Asian (EAS) AF: 0.278 AC: 1434 AN: 5166

South Asian (SAS) AF: 0.131 AC: 631 AN: 4824

European-Finnish (FIN) AF: 0.0599 AC: 634 AN: 10576

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0798 AC: 5415 AN: 67852

Other (OTH) AF: 0.0722 AC: 152 AN: 2106

Alfa AF: 0.0610 Hom.: 142

Bravo AF: 0.0659

TwinsUK AF: 0.0825 AC: 306

ALSPAC AF: 0.0745 AC: 287

ESP6500AA AF: 0.0209 AC: 92

ESP6500EA AF: 0.0791 AC: 680

ExAC AF: 0.0941 AC: 11425

Asia WGS AF: 0.181 AC: 631 AN: 3476

EpiCase AF: 0.0805

EpiControl AF: 0.0850

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.030
DANN	Benign	0.25
DEOGEN2	Benign	0.00064	T;T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.44	.;.;T
MetaRNN	Benign	0.0068	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.4	L;L;L
PhyloP100		-0.062
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.13	N;N;.
REVEL	Benign	0.045
Sift	Benign	0.72	T;T;.
Sift4G	Benign	1.0	T;T;T
Polyphen		0.049	B;B;B
Vest4		0.057
MPC		0.014
ClinPred		0.0018	T
GERP RS		-6.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.029
gMVP		0.11
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: rs4721888; hg19: chr7-20201395; COSMIC: COSV60541462; COSMIC: COSV60541462;