NM_005904.4:c.742+7065A>T

Variant names:

• chr18-48935416-T-A
• rs7238442
• NM_005904.4:c.742+7065A>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_005904.4(SMAD7):​c.742+7065A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 152,148 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0017 (0 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS2: High AC in GnomAd4 at 259 AD gene.

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.742+7065A>T		intron	N/A	NP_005895.1
	SMAD7	NM_001190821.2		c.739+7065A>T		intron	N/A	NP_001177750.1
	SMAD7	NM_001190823.2		c.178+7065A>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.742+7065A>T		intron	N/A	ENSP00000262158.2
	SMAD7	ENST00000589634.1	TSL:4	c.739+7065A>T		intron	N/A	ENSP00000467621.1
	SMAD7	ENST00000591805.5	TSL:2	c.97+7065A>T		intron	N/A	ENSP00000466902.1

Frequencies

GnomAD3 genomes AF: 0.00167 AC: 254 AN: 152030 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00560

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00239

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

GnomAD4 genome AF: 0.00170 AC: 259 AN: 152148 Hom.: 0 Cov.: 31 AF XY: 0.00184 AC XY: 137 AN XY: 74388

African (AFR) AF: 0.00571 AC: 237 AN: 41522

American (AMR) AF: 0.00111 AC: 17 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67962

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00 Hom.: 49788

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.26
DANN	Benign	0.77
PhyloP100		-1.6

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;