18-48927093-T-C

Position:

• chr18-48927093-T-C

Variant summary

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

The NM_005904.4(SMAD7):​c.743-5183A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 152,012 control chromosomes in the GnomAD database, including 25,529 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 0.57 (25529 hom., cov: 32)
• Consequence: SMAD7 NM_005904.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.513

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=-0.72).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMAD7	NM_005904.4	c.743-5183A>G		intron_variant		ENST00000262158.8	NP_005895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMAD7	ENST00000262158.8	c.743-5183A>G		intron_variant		1	NM_005904.4	ENSP00000262158	P4

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86699 AN: 151894 Hom.: 25490 Cov.: 32

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.700

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.539

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

GnomAD4 genome AF: 0.571 AC: 86794 AN: 152012 Hom.: 25529 Cov.: 32 AF XY: 0.577 AC XY: 42909 AN XY: 74304

Gnomad4 AFR AF: 0.685

Gnomad4 AMR AF: 0.626

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.701

Gnomad4 SAS AF: 0.705

Gnomad4 FIN AF: 0.531

Gnomad4 NFE AF: 0.485

Gnomad4 OTH AF: 0.544

Alfa AF: 0.504 Hom.: 45766

Bravo AF: 0.580

Asia WGS AF: 0.693 AC: 2407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	11
DANN	Benign	0.92

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: rs4939827; hg19: chr18-46453463; COSMIC: COSV50988825;