Variant 4-145515134-CTGTG-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_005900.3(SMAD1):c.400+161_400+164delGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0378 in 530,916 control chromosomes in the GnomAD database, including 69 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.024 ( 64 hom., cov: 0)

Exomes 𝑓: 0.043 ( 5 hom. )

Consequence

SMAD1
NM_005900.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.377

Variant links:

Genes affected

SMAD1 (HGNC:6767): (SMAD family member 1) The protein encoded by this gene belongs to the SMAD, a family of proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways. This protein mediates the signals of the bone morphogenetic proteins (BMPs), which are involved in a range of biological activities including cell growth, apoptosis, morphogenesis, development and immune responses. In response to BMP ligands, this protein can be phosphorylated and activated by the BMP receptor kinase. The phosphorylated form of this protein forms a complex with SMAD4, which is important for its function in the transcription regulation. This protein is a target for SMAD-specific E3 ubiquitin ligases, such as SMURF1 and SMURF2, and undergoes ubiquitination and proteasome-mediated degradation. Alternatively spliced transcript variants encoding the same protein have been observed. [provided by RefSeq, Jul 2008]

SMAD1 links:

SMAD1-AS1 (HGNC:49379): (SMAD1 antisense RNA 1)

SMAD1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 4-145515134-CTGTG-C is Benign according to our data. Variant chr4-145515134-CTGTG-C is described in ClinVar as [Benign]. Clinvar id is 1226228.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMAD1	NM_005900.3 link	c.400+161_400+164delGTGT		intron_variant		ENST00000302085.9	NP_005891.1	Q15797-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
SMAD1	ENST00000302085.9 link	c.400+122_400+125delTGTG	intron_variant	1	NM_005900.3	ENSP00000305769.4	Q15797-1
SMAD1	ENST00000394092.6 link	c.400+122_400+125delTGTG	intron_variant	1		ENSP00000377652.2	Q15797-1
SMAD1	ENST00000515385.1 link	c.400+122_400+125delTGTG	intron_variant	2		ENSP00000426568.1	Q15797-1
SMAD1-AS1	ENST00000513542.1 link	n.106-148_106-145delCACA	intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0238

AC:

3272

AN:

137226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0636

Gnomad AMI

AF:

0.0255

Gnomad AMR

AF:

0.0154

Gnomad ASJ

AF:

0.000916

Gnomad EAS

AF:

0.0149

Gnomad SAS

AF:

0.0113

Gnomad FIN

AF:

0.0153

Gnomad MID

AF:

0.00699

Gnomad NFE

AF:

0.00701

Gnomad OTH

AF:

0.0143

GnomAD4 exome

AF:

0.0426

AC:

16764

AN:

393598

Hom.:

AF XY:

0.0424

AC XY:

8659

AN XY:

204002

show subpopulations

Gnomad4 AFR exome

AF:

0.0593

Gnomad4 AMR exome

AF:

0.0659

Gnomad4 ASJ exome

AF:

0.0637

Gnomad4 EAS exome

AF:

0.105

Gnomad4 SAS exome

AF:

0.0321

Gnomad4 FIN exome

AF:

0.0376

Gnomad4 NFE exome

AF:

0.0347

Gnomad4 OTH exome

AF:

0.0509

GnomAD4 genome

AF:

0.0240

AC:

3296

AN:

137318

Hom.:

Cov.:

AF XY:

0.0242

AC XY:

1599

AN XY:

66026

show subpopulations

Gnomad4 AFR

AF:

0.0640

Gnomad4 AMR

AF:

0.0154

Gnomad4 ASJ

AF:

0.000916

Gnomad4 EAS

AF:

0.0152

Gnomad4 SAS

AF:

0.0111

Gnomad4 FIN

AF:

0.0153

Gnomad4 NFE

AF:

0.00701

Gnomad4 OTH

AF:

0.0142

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

GeneDx

May 24, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

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