rs10275612

Variant names:

• chr7-20142713-G-A
• rs10275612
• NM_182762.4:c.2347-1555C>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.2347-1555C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 152,032 control chromosomes in the GnomAD database, including 35,270 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 0.67 (35270 hom., cov: 32)
• Consequence: MACC1 NM_182762.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.222
• Publications: 10 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]

MACC1-AS1 (HGNC:41257): (MACC1 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACC1	NM_182762.4	c.2347-1555C>T		intron_variant	Intron 6 of 6	ENST00000400331.10	NP_877439.3
MACC1-AS1	NR_046756.1	n.105+693G>A		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACC1	ENST00000400331.10	c.2347-1555C>T		intron_variant	Intron 6 of 6	2	NM_182762.4	ENSP00000383185.3

Frequencies

GnomAD3 genomes AF: 0.672 AC: 102076 AN: 151914 Hom.: 35207 Cov.: 32

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.594

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.865

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.677

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

GnomAD4 genome AF: 0.672 AC: 102202 AN: 152032 Hom.: 35270 Cov.: 32 AF XY: 0.674 AC XY: 50061 AN XY: 74302

African (AFR) AF: 0.816 AC: 33855 AN: 41514

American (AMR) AF: 0.692 AC: 10575 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 2150 AN: 3462

East Asian (EAS) AF: 0.865 AC: 4467 AN: 5166

South Asian (SAS) AF: 0.675 AC: 3249 AN: 4810

European-Finnish (FIN) AF: 0.609 AC: 6424 AN: 10552

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39342 AN: 67940

Other (OTH) AF: 0.682 AC: 1440 AN: 2112

Alfa AF: 0.617 Hom.: 81589

Bravo AF: 0.685

Asia WGS AF: 0.783 AC: 2726 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	8.4
DANN	Benign	0.50
PhyloP100		0.22
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: rs10275612; hg19: chr7-20182336;