rs10275320

Positions:

• chr7-20142431-G-A
• chr7-20142431-G-T

Variant summary

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

The NM_182762.4(MACC1):​c.2347-1273C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0998 in 152,192 control chromosomes in the GnomAD database, including 918 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 0.10 (918 hom., cov: 32)
• Consequence: MACC1 NM_182762.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.278

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MACC1	NM_182762.4	c.2347-1273C>T		intron_variant		ENST00000400331.10
MACC1-AS1	NR_046756.1	n.105+411G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MACC1	ENST00000400331.10	c.2347-1273C>T		intron_variant		2	NM_182762.4	P1
MACC1	ENST00000332878.8	c.2347-1273C>T		intron_variant		1		P1
MACC1-AS1	ENST00000439285.1	n.105+411G>A		intron_variant, non_coding_transcript_variant		3
MACC1	ENST00000589011.1	c.2347-1273C>T		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.0998 AC: 15179 AN: 152074 Hom.: 917 Cov.: 32

Gnomad AFR AF: 0.0376

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.0273

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0630

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.0998 AC: 15196 AN: 152192 Hom.: 918 Cov.: 32 AF XY: 0.0979 AC XY: 7283 AN XY: 74408

Gnomad4 AFR AF: 0.0377

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.0272

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.0630

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.142

Alfa AF: 0.101 Hom.: 115

Bravo AF: 0.105

Asia WGS AF: 0.0680 AC: 237 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	6.5
DANN	Benign	0.70

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: rs10275320; hg19: chr7-20182054;