rs17186485

Variant names:

• chr18-48922662-G-A
• rs17186485
• NM_005904.4:c.743-752C>T

Variant summary

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

The NM_005904.4(SMAD7):​c.743-752C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0684 in 152,096 control chromosomes in the GnomAD database, including 389 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 0.068 (389 hom., cov: 32)
• Consequence: SMAD7 NM_005904.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.248
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0892 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.743-752C>T		intron	N/A	NP_005895.1
	SMAD7	NM_001190821.2		c.740-752C>T		intron	N/A	NP_001177750.1
	SMAD7	NM_001190823.2		c.179-752C>T		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.743-752C>T		intron	N/A	ENSP00000262158.2
	SMAD7	ENST00000589634.1	TSL:4	c.740-752C>T		intron	N/A	ENSP00000467621.1
	SMAD7	ENST00000591805.5	TSL:2	c.98-752C>T		intron	N/A	ENSP00000466902.1

Frequencies

GnomAD3 genomes AF: 0.0684 AC: 10388 AN: 151976 Hom.: 383 Cov.: 32

Gnomad AFR AF: 0.0915

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0561

Gnomad ASJ AF: 0.0854

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0583

Gnomad FIN AF: 0.0310

Gnomad MID AF: 0.0478

Gnomad NFE AF: 0.0686

Gnomad OTH AF: 0.0597

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

GnomAD4 genome AF: 0.0684 AC: 10402 AN: 152096 Hom.: 389 Cov.: 32 AF XY: 0.0654 AC XY: 4867 AN XY: 74366

African (AFR) AF: 0.0917 AC: 3802 AN: 41470

American (AMR) AF: 0.0559 AC: 855 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0854 AC: 296 AN: 3468

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5158

South Asian (SAS) AF: 0.0586 AC: 282 AN: 4816

European-Finnish (FIN) AF: 0.0310 AC: 329 AN: 10602

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0686 AC: 4663 AN: 67970

Other (OTH) AF: 0.0591 AC: 125 AN: 2116

Alfa AF: 0.0722 Hom.: 891

Bravo AF: 0.0716

Asia WGS AF: 0.0320 AC: 114 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.2
DANN	Benign	0.69
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs17186485; hg19: chr18-46449032;