15-66719608-T-C

Variant summary

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

The NM_005585.5(SMAD6):​c.952+3110T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 152,158 control chromosomes in the GnomAD database, including 45,970 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 0.77 ( 45970 hom., cov: 32)

Consequence

SMAD6
NM_005585.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.114
Variant links:
Genes affected
SMAD6 (HGNC:6772): (SMAD family member 6) The protein encoded by this gene belongs to the SMAD family of proteins, which are related to Drosophila 'mothers against decapentaplegic' (Mad) and C. elegans Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways. This protein functions in the negative regulation of BMP and TGF-beta/activin-signalling. Multiple transcript variants have been found for this gene.[provided by RefSeq, Sep 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=-0.91).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SMAD6NM_005585.5 linkuse as main transcriptc.952+3110T>C intron_variant ENST00000288840.10 NP_005576.3 O43541-1
SMAD6XM_011521561.3 linkuse as main transcriptc.169+3110T>C intron_variant XP_011519863.1 O43541-2
SMAD6NR_027654.2 linkuse as main transcriptn.2107+2468T>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SMAD6ENST00000288840.10 linkuse as main transcriptc.952+3110T>C intron_variant 1 NM_005585.5 ENSP00000288840.5 O43541-1
SMAD6ENST00000557916.5 linkuse as main transcriptn.*67+2468T>C intron_variant 1 ENSP00000452955.1 O43541-4
SMAD6ENST00000559931.5 linkuse as main transcriptn.*67+2468T>C intron_variant 3 ENSP00000453446.1 H0YM33

Frequencies

GnomAD3 genomes
AF:
0.773
AC:
117452
AN:
152040
Hom.:
45914
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.884
Gnomad AMI
AF:
0.743
Gnomad AMR
AF:
0.803
Gnomad ASJ
AF:
0.672
Gnomad EAS
AF:
0.953
Gnomad SAS
AF:
0.752
Gnomad FIN
AF:
0.732
Gnomad MID
AF:
0.633
Gnomad NFE
AF:
0.698
Gnomad OTH
AF:
0.780
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.773
AC:
117569
AN:
152158
Hom.:
45970
Cov.:
32
AF XY:
0.776
AC XY:
57743
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.884
Gnomad4 AMR
AF:
0.803
Gnomad4 ASJ
AF:
0.672
Gnomad4 EAS
AF:
0.953
Gnomad4 SAS
AF:
0.752
Gnomad4 FIN
AF:
0.732
Gnomad4 NFE
AF:
0.698
Gnomad4 OTH
AF:
0.780
Alfa
AF:
0.644
Hom.:
1797
Bravo
AF:
0.786
Asia WGS
AF:
0.846
AC:
2943
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
3.2
DANN
Benign
0.41

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: rs2119260; hg19: chr15-67011946; API