7-20212017-T-C

Variant names:

• chr7-20212017-T-C
• rs3095009
• NM_182762.4:c.-218+5282A>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.-218+5282A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 151,998 control chromosomes in the GnomAD database, including 20,137 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 0.51 (20137 hom., cov: 32)
• Consequence: MACC1 NM_182762.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.602
• Publications: 4 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]

GIRGL (HGNC:55702): (glutamine insufficiency regulator of glutaminase lncRNA)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACC1	NM_182762.4	c.-218+5282A>G		intron_variant	Intron 1 of 6	ENST00000400331.10	NP_877439.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACC1	ENST00000400331.10	c.-218+5282A>G		intron_variant	Intron 1 of 6	2	NM_182762.4	ENSP00000383185.3

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76894 AN: 151878 Hom.: 20116 Cov.: 32

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.880

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.517

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

GnomAD4 genome AF: 0.506 AC: 76971 AN: 151998 Hom.: 20137 Cov.: 32 AF XY: 0.509 AC XY: 37808 AN XY: 74318

African (AFR) AF: 0.542 AC: 22475 AN: 41454

American (AMR) AF: 0.573 AC: 8748 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.527 AC: 1827 AN: 3470

East Asian (EAS) AF: 0.880 AC: 4556 AN: 5178

South Asian (SAS) AF: 0.594 AC: 2859 AN: 4814

European-Finnish (FIN) AF: 0.402 AC: 4244 AN: 10552

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.450 AC: 30607 AN: 67950

Other (OTH) AF: 0.515 AC: 1086 AN: 2108

Alfa AF: 0.476 Hom.: 25545

Bravo AF: 0.520

Asia WGS AF: 0.692 AC: 2394 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.38
DANN	Benign	0.42
PhyloP100		-0.60
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: rs3095009; hg19: chr7-20251640;