rs10275320

Variant names:

• chr7-20142431-G-A
• rs10275320
• NM_182762.4:c.2347-1273C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-20142431-G-A
• chr7-20142431-G-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.2347-1273C>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
• Publications: 2 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=-0.84).
• 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 rank	MANE	Protein	UniProt
MACC1	NM_182762.4	c.2347-1273C>T		intron_variant	Intron 6 of 6	ENST00000400331.10	NP_877439.3
MACC1-AS1	NR_046756.1	n.105+411G>A		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACC1	ENST00000400331.10	c.2347-1273C>T		intron_variant	Intron 6 of 6	2	NM_182762.4	ENSP00000383185.3

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

African (AFR) AF: 0.0377 AC: 1565 AN: 41536

American (AMR) AF: 0.161 AC: 2466 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 487 AN: 3470

East Asian (EAS) AF: 0.0272 AC: 141 AN: 5184

South Asian (SAS) AF: 0.105 AC: 504 AN: 4820

European-Finnish (FIN) AF: 0.0630 AC: 668 AN: 10598

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8870 AN: 67986

Other (OTH) AF: 0.142 AC: 301 AN: 2116

Alfa AF: 0.0988 Hom.: 117

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
PhyloP100		0.28
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: rs10275320; hg19: chr7-20182054;