18-48930726-T-C

Position:

• chr18-48930726-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005904.4(SMAD7):​c.743-8816A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.862 in 152,144 control chromosomes in the GnomAD database, including 56,735 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 0.86 (56735 hom., cov: 33)
• Consequence: SMAD7 NM_005904.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMAD7	NM_005904.4	c.743-8816A>G		intron_variant		ENST00000262158.8	NP_005895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMAD7	ENST00000262158.8	c.743-8816A>G		intron_variant		1	NM_005904.4	ENSP00000262158	P4

Frequencies

GnomAD3 genomes AF: 0.862 AC: 131099 AN: 152026 Hom.: 56681 Cov.: 33

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.917

Gnomad ASJ AF: 0.929

Gnomad EAS AF: 0.877

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.916

Gnomad MID AF: 0.933

Gnomad NFE AF: 0.867

Gnomad OTH AF: 0.883

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

GnomAD4 genome AF: 0.862 AC: 131210 AN: 152144 Hom.: 56735 Cov.: 33 AF XY: 0.862 AC XY: 64137 AN XY: 74370

Gnomad4 AFR AF: 0.827

Gnomad4 AMR AF: 0.917

Gnomad4 ASJ AF: 0.929

Gnomad4 EAS AF: 0.877

Gnomad4 SAS AF: 0.765

Gnomad4 FIN AF: 0.916

Gnomad4 NFE AF: 0.867

Gnomad4 OTH AF: 0.885

Alfa AF: 0.865 Hom.: 35169

Bravo AF: 0.864

Asia WGS AF: 0.828 AC: 2882 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.6
DANN	Benign	0.096

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

Publications

LitVar

Other links and lift over

dbSNP: rs12456328; hg19: chr18-46457096;