rs1990172

Positions:

• chr7-20164512-A-C
• chr7-20164512-A-G

Variant summary

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

The NM_182762.4(MACC1):​c.-152-113T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 152,052 control chromosomes in the GnomAD database, including 7,121 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 0.28 (7121 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MACC1 NM_182762.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MACC1	NM_182762.4	c.-152-113T>G		intron_variant		ENST00000400331.10	NP_877439.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MACC1	ENST00000400331.10	c.-152-113T>G		intron_variant		2	NM_182762.4	ENSP00000383185.3
MACC1	ENST00000332878.8	c.-8-2642T>G		intron_variant		1		ENSP00000328410.4
MACC1	ENST00000589011.1	c.-8-2642T>G		intron_variant		5		ENSP00000466864.1
MACC1	ENST00000471019.1	n.274-113T>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41984 AN: 151934 Hom.: 7120 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.283

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 4 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.276 AC: 42005 AN: 152052 Hom.: 7121 Cov.: 32 AF XY: 0.286 AC XY: 21269 AN XY: 74318

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.357

Gnomad4 EAS AF: 0.834

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.285

Alfa AF: 0.277 Hom.: 7931

Bravo AF: 0.275

Asia WGS AF: 0.604 AC: 2100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.3
DANN	Benign	0.84

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: rs1990172; hg19: chr7-20204135;