chr7-20193649-C-A

Position:

• chr7-20193649-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182762.4(MACC1):​c.-217-22871G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,194 control chromosomes in the GnomAD database, including 1,790 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 0.15 (1790 hom., cov: 32)
• Consequence: MACC1 NM_182762.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.645

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MACC1	NM_182762.4	c.-217-22871G>T		intron_variant		ENST00000400331.10	NP_877439.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MACC1	ENST00000400331.10	c.-217-22871G>T		intron_variant		2	NM_182762.4	ENSP00000383185	P1
MACC1	ENST00000332878.8	c.-9+23650G>T		intron_variant		1		ENSP00000328410	P1
MACC1	ENST00000471019.1	n.205+4876G>T		intron_variant, non_coding_transcript_variant		3
MACC1	ENST00000483317.1	n.55-22868G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22670 AN: 152074 Hom.: 1782 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.0373

Gnomad SAS AF: 0.0690

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.149 AC: 22699 AN: 152194 Hom.: 1790 Cov.: 32 AF XY: 0.147 AC XY: 10955 AN XY: 74410

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.0376

Gnomad4 SAS AF: 0.0682

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.155

Alfa AF: 0.145 Hom.: 859

Bravo AF: 0.147

Asia WGS AF: 0.101 AC: 351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.3
DANN	Benign	0.31

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

Other links and lift over

dbSNP: rs7780032; hg19: chr7-20233272;