rs3095007

Variant names:

• chr7-20216726-A-C
• rs3095007
• NM_182762.4:c.-218+573T>G

Your query was ambiguous. Multiple possible variants found:

• chr7-20216726-A-C
• chr7-20216726-A-T

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+573T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 151,952 control chromosomes in the GnomAD database, including 40,381 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 0.73 (40381 hom., cov: 31)
• Consequence: MACC1 NM_182762.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 7 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACC1	NM_182762.4	c.-218+573T>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+573T>G		intron_variant	Intron 1 of 6	2	NM_182762.4	ENSP00000383185.3

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110359 AN: 151832 Hom.: 40337 Cov.: 31

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.781

Gnomad ASJ AF: 0.758

Gnomad EAS AF: 0.914

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.669

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.738

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

GnomAD4 genome AF: 0.727 AC: 110459 AN: 151952 Hom.: 40381 Cov.: 31 AF XY: 0.726 AC XY: 53900 AN XY: 74266

African (AFR) AF: 0.739 AC: 30636 AN: 41434

American (AMR) AF: 0.782 AC: 11936 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.758 AC: 2629 AN: 3468

East Asian (EAS) AF: 0.914 AC: 4736 AN: 5182

South Asian (SAS) AF: 0.654 AC: 3150 AN: 4816

European-Finnish (FIN) AF: 0.650 AC: 6864 AN: 10552

Middle Eastern (MID) AF: 0.664 AC: 194 AN: 292

European-Non Finnish (NFE) AF: 0.708 AC: 48105 AN: 67924

Other (OTH) AF: 0.741 AC: 1563 AN: 2110

Alfa AF: 0.716 Hom.: 5872

Bravo AF: 0.740

Asia WGS AF: 0.799 AC: 2778 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	1.5
DANN	Benign	0.61
PhyloP100		-1.3
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: rs3095007; hg19: chr7-20256349;