18-48935416-T-C

Variant names:

• chr18-48935416-T-C
• rs7238442
• NM_005904.4:c.742+7065A>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+7065A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 152,088 control chromosomes in the GnomAD database, including 28,418 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 0.58 (28418 hom., cov: 31)
• Consequence: SMAD7 NM_005904.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63
• Publications: 15 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMAD7	NM_005904.4	c.742+7065A>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+7065A>G		intron_variant	Intron 3 of 3	1	NM_005904.4	ENSP00000262158.2

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88093 AN: 151970 Hom.: 28362 Cov.: 31

Gnomad AFR AF: 0.882

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.569

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

GnomAD4 genome AF: 0.580 AC: 88206 AN: 152088 Hom.: 28418 Cov.: 31 AF XY: 0.577 AC XY: 42872 AN XY: 74358

African (AFR) AF: 0.882 AC: 36613 AN: 41506

American (AMR) AF: 0.489 AC: 7476 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1961 AN: 3470

East Asian (EAS) AF: 0.508 AC: 2625 AN: 5168

South Asian (SAS) AF: 0.519 AC: 2496 AN: 4810

European-Finnish (FIN) AF: 0.451 AC: 4775 AN: 10586

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.450 AC: 30551 AN: 67940

Other (OTH) AF: 0.573 AC: 1211 AN: 2112

Alfa AF: 0.475 Hom.: 49788

Bravo AF: 0.597

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.31
DANN	Benign	0.54
PhyloP100		-1.6
Mutation Taster		=98/2	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: rs7238442; hg19: chr18-46461786;