Variant 18-48948427-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_005904.4(SMAD7):c.624C>T(p.Pro208=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000993 in 1,595,338 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. P208P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00082 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 5 hom. )

Consequence

SMAD7
NM_005904.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.412

Variant links:

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]

SMAD7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 18-48948427-G-A is Benign according to our data. Variant chr18-48948427-G-A is described in ClinVar as [Benign]. Clinvar id is 786841.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.412 with no splicing effect.

BS2

High AC in GnomAd4 at 125 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SMAD7	NM_005904.4 linkuse as main transcript	c.624C>T	p.Pro208=	synonymous_variant	2/4	ENST00000262158.8
SMAD7	NM_001190821.2 linkuse as main transcript	c.624C>T	p.Pro208=	synonymous_variant	2/4
SMAD7	NM_001190822.2 linkuse as main transcript	c.-22C>T		5_prime_UTR_variant	2/4
SMAD7	XM_047437509.1 linkuse as main transcript	c.-22C>T		5_prime_UTR_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMAD7	ENST00000262158.8 linkuse as main transcript	c.624C>T	p.Pro208=	synonymous_variant	2/4	1	NM_005904.4	P4	O15105-1
SMAD7	ENST00000589634.1 linkuse as main transcript	c.624C>T	p.Pro208=	synonymous_variant	2/4	4		A1	O15105-3
SMAD7	ENST00000586093.1 linkuse as main transcript	c.-22C>T		5_prime_UTR_variant	1/3	2
SMAD7	ENST00000591805.5 linkuse as main transcript	c.-22C>T		5_prime_UTR_variant	2/4	2			O15105-2

Frequencies

GnomAD3 genomes

AF:

0.000821

AC:

125

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000632

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00148

AC:

347

AN:

234504

Hom.:

AF XY:

0.00126

AC XY:

161

AN XY:

127280

show subpopulations

Gnomad AFR exome

AF:

0.000265

Gnomad AMR exome

AF:

0.00152

Gnomad ASJ exome

AF:

0.0184

Gnomad EAS exome

AF:

0.0000604

Gnomad SAS exome

AF:

0.0000741

Gnomad FIN exome

AF:

0.000187

Gnomad NFE exome

AF:

0.000831

Gnomad OTH exome

AF:

0.00353

GnomAD4 exome

AF:

0.00101

AC:

1459

AN:

1442986

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

723

AN XY:

717910

show subpopulations

Gnomad4 AFR exome

AF:

0.000125

Gnomad4 AMR exome

AF:

0.00179

Gnomad4 ASJ exome

AF:

0.0170

Gnomad4 EAS exome

AF:

0.0000256

Gnomad4 SAS exome

AF:

0.0000846

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000741

Gnomad4 OTH exome

AF:

0.00166

GnomAD4 genome

AF:

0.000820

AC:

125

AN:

152352

Hom.:

Cov.:

AF XY:

0.000792

AC XY:

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.000264

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.0118

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000632

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00241

Hom.:

Bravo

AF:

0.000922

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

5.0

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over