18-48922741-T-C

Variant names:

• chr18-48922741-T-C
• rs8085824
• NM_005904.4:c.743-831A>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.743-831A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 151,802 control chromosomes in the GnomAD database, including 10,296 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 0.36 (10296 hom., cov: 30)
• Consequence: SMAD7 NM_005904.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.725
• 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=-0.63).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005904.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMAD7	NM_005904.4	MANE Select	c.743-831A>G		intron	N/A	NP_005895.1
	SMAD7	NM_001190821.2		c.740-831A>G		intron	N/A	NP_001177750.1
	SMAD7	NM_001190823.2		c.179-831A>G		intron	N/A	NP_001177752.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMAD7	ENST00000262158.8	TSL:1 MANE Select	c.743-831A>G		intron	N/A	ENSP00000262158.2
	SMAD7	ENST00000589634.1	TSL:4	c.740-831A>G		intron	N/A	ENSP00000467621.1
	SMAD7	ENST00000591805.5	TSL:2	c.98-831A>G		intron	N/A	ENSP00000466902.1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54229 AN: 151684 Hom.: 10298 Cov.: 30

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.357 AC: 54228 AN: 151802 Hom.: 10296 Cov.: 30 AF XY: 0.349 AC XY: 25900 AN XY: 74178

African (AFR) AF: 0.252 AC: 10437 AN: 41420

American (AMR) AF: 0.329 AC: 5018 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1687 AN: 3464

East Asian (EAS) AF: 0.294 AC: 1503 AN: 5120

South Asian (SAS) AF: 0.251 AC: 1209 AN: 4812

European-Finnish (FIN) AF: 0.361 AC: 3804 AN: 10536

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.431 AC: 29218 AN: 67868

Other (OTH) AF: 0.395 AC: 831 AN: 2102

Alfa AF: 0.405 Hom.: 7601

Bravo AF: 0.352

Asia WGS AF: 0.262 AC: 912 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.6
DANN	Benign	0.81
PhyloP100		0.72
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: rs8085824; hg19: chr18-46449111;