Genetic Variant SMAD5:c.1254+109C>G (chr5-136174741-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005903.7(SMAD5):c.1254+109C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0926 in 714,996 control chromosomes in the GnomAD database, including 3,941 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 0.095 ( 824 hom., cov: 32)

Exomes 𝑓: 0.092 ( 3117 hom. )

Consequence

SMAD5
NM_005903.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.16

Variant links:

Genes affected

SMAD5 (HGNC:6771): (SMAD family member 5) The protein encoded by this gene is involved in the transforming growth factor beta signaling pathway that results in an inhibition of the proliferation of hematopoietic progenitor cells. The encoded protein is activated by bone morphogenetic proteins type 1 receptor kinase, and may be involved in cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

SMAD5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMAD5	NM_005903.7 link	c.1254+109C>G		intron_variant	Intron 7 of 7	ENST00000545279.6	NP_005894.3	Q99717Q68DB7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMAD5	ENST00000545279.6 link	c.1254+109C>G		intron_variant	Intron 7 of 7	1	NM_005903.7	ENSP00000441954.2		Q99717

Frequencies

GnomAD3 genomes

AF:

0.0952

AC:

14455

AN:

151842

Hom.:

824

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.0956

Gnomad ASJ

AF:

0.0576

Gnomad EAS

AF:

0.270

Gnomad SAS

AF:

0.0814

Gnomad FIN

AF:

0.138

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0754

Gnomad OTH

AF:

0.101

GnomAD4 exome

AF:

0.0919

AC:

51723

AN:

563036

Hom.:

3117

AF XY:

0.0904

AC XY:

26605

AN XY:

294424

show subpopulations

Gnomad4 AFR exome

AF:

0.104

Gnomad4 AMR exome

AF:

0.113

Gnomad4 ASJ exome

AF:

0.0620

Gnomad4 EAS exome

AF:

0.260

Gnomad4 SAS exome

AF:

0.0766

Gnomad4 FIN exome

AF:

0.130

Gnomad4 NFE exome

AF:

0.0730

Gnomad4 OTH exome

AF:

0.0925

GnomAD4 genome

AF:

0.0952

AC:

14473

AN:

151960

Hom.:

824

Cov.:

AF XY:

0.0990

AC XY:

7351

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.101

Gnomad4 AMR

AF:

0.0955

Gnomad4 ASJ

AF:

0.0576

Gnomad4 EAS

AF:

0.270

Gnomad4 SAS

AF:

0.0806

Gnomad4 FIN

AF:

0.138

Gnomad4 NFE

AF:

0.0754

Gnomad4 OTH

AF:

0.106

Alfa

AF:

0.0372

Hom.:

Bravo

AF:

0.0961

Asia WGS

AF:

0.204

AC:

712

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.5

DANN

Benign

0.60

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over