18-48923195-C-G

Variant names:

• chr18-48923195-C-G
• rs58920878
• NM_005904.4:c.743-1285G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005904.4(SMAD7):​c.743-1285G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 152,122 control chromosomes in the GnomAD database, including 11,550 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 0.38 (11550 hom., cov: 32)
• Consequence: SMAD7 NM_005904.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.853
• Publications: 18 publications found

Genes affected

SMAD7 (HGNC:6773): (SMAD family member 7) The protein encoded by this gene is a nuclear protein that binds the E3 ubiquitin ligase SMURF2. Upon binding, this complex translocates to the cytoplasm, where it interacts with TGF-beta receptor type-1 (TGFBR1), leading to the degradation of both the encoded protein and TGFBR1. Expression of this gene is induced by TGFBR1. Variations in this gene are a cause of susceptibility to colorectal cancer type 3 (CRCS3). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMAD7	NM_005904.4	c.743-1285G>C		intron_variant	Intron 3 of 3	ENST00000262158.8	NP_005895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMAD7	ENST00000262158.8	c.743-1285G>C		intron_variant	Intron 3 of 3	1	NM_005904.4	ENSP00000262158.2

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58260 AN: 152004 Hom.: 11553 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.423

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

GnomAD4 genome AF: 0.383 AC: 58268 AN: 152122 Hom.: 11550 Cov.: 32 AF XY: 0.374 AC XY: 27814 AN XY: 74350

African (AFR) AF: 0.323 AC: 13392 AN: 41506

American (AMR) AF: 0.340 AC: 5201 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1710 AN: 3466

East Asian (EAS) AF: 0.293 AC: 1516 AN: 5170

South Asian (SAS) AF: 0.259 AC: 1248 AN: 4822

European-Finnish (FIN) AF: 0.364 AC: 3850 AN: 10580

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.440 AC: 29925 AN: 67970

Other (OTH) AF: 0.417 AC: 882 AN: 2114

Alfa AF: 0.265 Hom.: 633

Bravo AF: 0.381

Asia WGS AF: 0.269 AC: 939 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.6
DANN	Benign	0.68
PhyloP100		0.85
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: rs58920878; hg19: chr18-46449565; COSMIC: COSV107257860;