18-48946306-G-T

Variant names:

• chr18-48946306-G-T
• rs1316447
• NM_005904.4:c.667+2078C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005904.4(SMAD7):​c.667+2078C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: SMAD7 NM_005904.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.976
• Publications: 10 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMAD7	NM_005904.4	c.667+2078C>A		intron_variant	Intron 2 of 3	ENST00000262158.8	NP_005895.1
SMAD7	NM_001190821.2	c.667+2078C>A		intron_variant	Intron 2 of 3		NP_001177750.1
SMAD7	NM_001190822.2	c.22+2078C>A		intron_variant	Intron 2 of 3		NP_001177751.1
SMAD7	XM_047437509.1	c.22+2078C>A		intron_variant	Intron 2 of 3		XP_047293465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMAD7	ENST00000262158.8	c.667+2078C>A		intron_variant	Intron 2 of 3	1	NM_005904.4	ENSP00000262158.2
SMAD7	ENST00000589634.1	c.667+2078C>A		intron_variant	Intron 2 of 3	4		ENSP00000467621.1
SMAD7	ENST00000591805.5	c.22+2078C>A		intron_variant	Intron 2 of 3	2		ENSP00000466902.1
SMAD7	ENST00000586093.1	c.22+2078C>A		intron_variant	Intron 1 of 2	2		ENSP00000465590.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	7.8
DANN	Benign	0.63
PhyloP100		0.98

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: rs1316447; hg19: chr18-46472676;