chr18-48926786-A-T

Variant names:

• chr18-48926786-A-T
• rs11874392
• NM_005904.4:c.743-4876T>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005904.4(SMAD7):​c.743-4876T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 152,016 control chromosomes in the GnomAD database, including 19,530 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 0.50 (19530 hom., cov: 32)
• Consequence: SMAD7 NM_005904.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174
• Publications: 32 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMAD7	NM_005904.4	c.743-4876T>A		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.743-4876T>A		intron_variant	Intron 3 of 3	1	NM_005904.4	ENSP00000262158.2

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76568 AN: 151898 Hom.: 19499 Cov.: 32

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.504 AC: 76646 AN: 152016 Hom.: 19530 Cov.: 32 AF XY: 0.511 AC XY: 37944 AN XY: 74300

African (AFR) AF: 0.532 AC: 22075 AN: 41456

American (AMR) AF: 0.533 AC: 8132 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1481 AN: 3468

East Asian (EAS) AF: 0.548 AC: 2829 AN: 5166

South Asian (SAS) AF: 0.688 AC: 3317 AN: 4818

European-Finnish (FIN) AF: 0.499 AC: 5276 AN: 10578

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.470 AC: 31947 AN: 67942

Other (OTH) AF: 0.488 AC: 1032 AN: 2114

Alfa AF: 0.482 Hom.: 2347

Bravo AF: 0.501

Asia WGS AF: 0.622 AC: 2163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	2.5
DANN	Benign	0.72
PhyloP100		-0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs11874392; hg19: chr18-46453156;