rs3095008

Positions:

• chr7-20216082-G-A
• chr7-20216082-G-C

Variant summary

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

The NM_182762.4(MACC1):​c.-218+1217C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,874 control chromosomes in the GnomAD database, including 18,313 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 0.48 (18313 hom., cov: 31)
• Consequence: MACC1 NM_182762.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140

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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MACC1	NM_182762.4	c.-218+1217C>T		intron_variant		ENST00000400331.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MACC1	ENST00000400331.10	c.-218+1217C>T		intron_variant		2	NM_182762.4	P1
MACC1	ENST00000332878.8	c.-9+1217C>T		intron_variant		1		P1
MACC1	ENST00000471019.1	n.59+1217C>T		intron_variant, non_coding_transcript_variant		3
MACC1	ENST00000483317.1	n.54+1217C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72820 AN: 151756 Hom.: 18292 Cov.: 31

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.480 AC: 72889 AN: 151874 Hom.: 18313 Cov.: 31 AF XY: 0.482 AC XY: 35803 AN XY: 74208

Gnomad4 AFR AF: 0.492

Gnomad4 AMR AF: 0.584

Gnomad4 ASJ AF: 0.533

Gnomad4 EAS AF: 0.905

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.493

Alfa AF: 0.443 Hom.: 11133

Bravo AF: 0.498

Asia WGS AF: 0.701 AC: 2427 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.1
DANN	Benign	0.74

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: rs3095008; hg19: chr7-20255705;