rs4721888

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr7-20161772-G-A
• chr7-20161772-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_182762.4(MACC1):​c.91C>T​(p.Leu31Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,240 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L31V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MACC1 NM_182762.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0620

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04831788).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACC1	NM_182762.4	c.91C>T	p.Leu31Phe	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>T	p.Leu31Phe	missense_variant	Exon 4 of 7	2	NM_182762.4	ENSP00000383185.3
MACC1	ENST00000332878.8	c.91C>T	p.Leu31Phe	missense_variant	Exon 2 of 5	1		ENSP00000328410.4
MACC1	ENST00000589011.1	c.91C>T	p.Leu31Phe	missense_variant	Exon 2 of 5	5		ENSP00000466864.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459240 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726044

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.040
DANN	Benign	0.74
DEOGEN2	Benign	0.0021	T;T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.38	.;.;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.048	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.69	N;N;N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.47	N;N;.
REVEL	Benign	0.034
Sift	Benign	0.73	T;T;.
Sift4G	Benign	0.27	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.081
MutPred		0.13		Gain of methylation at K30 (P = 0.0457);Gain of methylation at K30 (P = 0.0457);Gain of methylation at K30 (P = 0.0457);
MVP		0.055
MPC		0.013
ClinPred		0.030	T
GERP RS		-6.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.031
gMVP		0.11

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-20201395;