rs4939832

chr18-48939295-A-G

Variant summary

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

The NM_005904.4(SMAD7):c.742+3186T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 150,992 control chromosomes in the GnomAD database, including 8,143 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 0.31 (8143 hom., cov: 28)
• Consequence: SMAD7 NM_005904.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.750

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMAD7	NM_005904.4	c.742+3186T>C		intron_variant		ENST00000262158.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMAD7	ENST00000262158.8	c.742+3186T>C		intron_variant		1	NM_005904.4	P4

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47317 AN: 150872 Hom.: 8120 Cov.: 28

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.314 AC: 47376 AN: 150992 Hom.: 8143 Cov.: 28 AF XY: 0.319 AC XY: 23482 AN XY: 73704

Gnomad4 AFR AF: 0.434

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.497

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.313

Alfa AF: 0.260 Hom.: 10858

Bravo AF: 0.317

Asia WGS AF: 0.498 AC: 1730 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	9.0
Dann	Benign	0.78

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: rs4939832; hg19: chr18-46465665;