chr7-20142713-G-A

Position:

• chr7-20142713-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• 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/exons	MANE	Protein	UniProt
MACC1	NM_182762.4	c.2347-1555C>T		intron_variant		ENST00000400331.10	NP_877439.3
MACC1-AS1	NR_046756.1	n.105+693G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MACC1	ENST00000400331.10	c.2347-1555C>T		intron_variant		2	NM_182762.4	ENSP00000383185	P1
MACC1	ENST00000332878.8	c.2347-1555C>T		intron_variant		1		ENSP00000328410	P1
MACC1-AS1	ENST00000439285.1	n.105+693G>A		intron_variant, non_coding_transcript_variant		3
MACC1	ENST00000589011.1	c.2347-1555C>T		intron_variant		5		ENSP00000466864	P1

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

Gnomad4 AFR AF: 0.816

Gnomad4 AMR AF: 0.692

Gnomad4 ASJ AF: 0.621

Gnomad4 EAS AF: 0.865

Gnomad4 SAS AF: 0.675

Gnomad4 FIN AF: 0.609

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.682

Alfa AF: 0.601 Hom.: 46486

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

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: rs10275612; hg19: chr7-20182336;