rs13179769

Variant summary

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

The NM_005903.7(SMAD5):​c.404-2685C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 151,736 control chromosomes in the GnomAD database, including 10,837 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 0.36 ( 10837 hom., cov: 31)

Consequence

SMAD5
NM_005903.7 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.42
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]

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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=-1.03).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SMAD5NM_005903.7 linkc.404-2685C>A intron_variant ENST00000545279.6 NP_005894.3 Q99717Q68DB7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SMAD5ENST00000545279.6 linkc.404-2685C>A intron_variant 1 NM_005903.7 ENSP00000441954.2 Q99717
SMAD5ENST00000509297.6 linkc.404-2685C>A intron_variant 1 ENSP00000426696.2 Q99717
SMAD5ENST00000545620.5 linkc.404-2685C>A intron_variant 5 ENSP00000446474.2 Q99717
SMAD5ENST00000514777.1 linkn.60-14263C>A intron_variant 3

Frequencies

GnomAD3 genomes
AF:
0.360
AC:
54639
AN:
151618
Hom.:
10808
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.538
Gnomad AMI
AF:
0.184
Gnomad AMR
AF:
0.285
Gnomad ASJ
AF:
0.343
Gnomad EAS
AF:
0.375
Gnomad SAS
AF:
0.186
Gnomad FIN
AF:
0.302
Gnomad MID
AF:
0.362
Gnomad NFE
AF:
0.292
Gnomad OTH
AF:
0.382
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.361
AC:
54714
AN:
151736
Hom.:
10837
Cov.:
31
AF XY:
0.356
AC XY:
26418
AN XY:
74152
show subpopulations
Gnomad4 AFR
AF:
0.539
Gnomad4 AMR
AF:
0.285
Gnomad4 ASJ
AF:
0.343
Gnomad4 EAS
AF:
0.376
Gnomad4 SAS
AF:
0.185
Gnomad4 FIN
AF:
0.302
Gnomad4 NFE
AF:
0.292
Gnomad4 OTH
AF:
0.384
Alfa
AF:
0.327
Hom.:
1439
Bravo
AF:
0.374

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.0040
DANN
Benign
0.54

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.

Other links and lift over

dbSNP: rs13179769; hg19: chr5-135493860; API