chr18-48941666-T-C

Variant names:

• chr18-48941666-T-C
• rs2337109
• NM_005904.4:c.742+815A>G

Variant summary

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

The NM_005904.4(SMAD7):​c.742+815A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,222 control chromosomes in the GnomAD database, including 5,094 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 0.18 (5094 hom., cov: 32)
• Consequence: SMAD7 NM_005904.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.647
• Publications: 2 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=-0.57).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMAD7	NM_005904.4	c.742+815A>G		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.742+815A>G		intron_variant	Intron 3 of 3	1	NM_005904.4	ENSP00000262158.2

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27671 AN: 152104 Hom.: 5068 Cov.: 32

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0700

Gnomad EAS AF: 0.0384

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.0317

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0604

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.182 AC: 27739 AN: 152222 Hom.: 5094 Cov.: 32 AF XY: 0.181 AC XY: 13497 AN XY: 74446

African (AFR) AF: 0.467 AC: 19389 AN: 41486

American (AMR) AF: 0.100 AC: 1537 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0700 AC: 243 AN: 3470

East Asian (EAS) AF: 0.0382 AC: 198 AN: 5190

South Asian (SAS) AF: 0.314 AC: 1513 AN: 4822

European-Finnish (FIN) AF: 0.0317 AC: 337 AN: 10622

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.0604 AC: 4109 AN: 68016

Other (OTH) AF: 0.159 AC: 337 AN: 2116

Alfa AF: 0.0936 Hom.: 783

Bravo AF: 0.193

Asia WGS AF: 0.199 AC: 695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	4.6
DANN	Benign	0.78
PhyloP100		-0.65
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: rs2337109; hg19: chr18-46468036;