chr15-66703215-C-T
Position:
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2
The NM_005585.5(SMAD6):c.-44C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0196 in 1,318,380 control chromosomes in the GnomAD database, including 333 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.015 ( 19 hom., cov: 33)
Exomes 𝑓: 0.020 ( 314 hom. )
Consequence
SMAD6
NM_005585.5 5_prime_UTR
NM_005585.5 5_prime_UTR
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 1.18
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -18 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.35).
BP6
Variant 15-66703215-C-T is Benign according to our data. Variant chr15-66703215-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1208555.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-66703215-C-T is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0148 (2255/152178) while in subpopulation NFE AF= 0.0227 (1541/67974). AF 95% confidence interval is 0.0217. There are 19 homozygotes in gnomad4. There are 1015 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 2255 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SMAD6 | NM_005585.5 | c.-44C>T | 5_prime_UTR_variant | 1/4 | ENST00000288840.10 | NP_005576.3 | ||
SMAD6 | NR_027654.2 | n.980C>T | non_coding_transcript_exon_variant | 1/5 | ||||
SMAD6 | XR_931827.3 | n.980C>T | non_coding_transcript_exon_variant | 1/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SMAD6 | ENST00000288840.10 | c.-44C>T | 5_prime_UTR_variant | 1/4 | 1 | NM_005585.5 | ENSP00000288840 | P1 | ||
SMAD6 | ENST00000612349.1 | n.139C>T | non_coding_transcript_exon_variant | 1/1 | ||||||
SMAD6 | ENST00000557916.5 | upstream_gene_variant | 1 | ENSP00000452955 |
Frequencies
GnomAD3 genomes AF: 0.0148 AC: 2256AN: 152070Hom.: 19 Cov.: 33
GnomAD3 genomes
AF:
AC:
2256
AN:
152070
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0159 AC: 541AN: 34100Hom.: 14 AF XY: 0.0150 AC XY: 275AN XY: 18354
GnomAD3 exomes
AF:
AC:
541
AN:
34100
Hom.:
AF XY:
AC XY:
275
AN XY:
18354
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0203 AC: 23628AN: 1166202Hom.: 314 Cov.: 21 AF XY: 0.0197 AC XY: 11152AN XY: 565456
GnomAD4 exome
AF:
AC:
23628
AN:
1166202
Hom.:
Cov.:
21
AF XY:
AC XY:
11152
AN XY:
565456
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0148 AC: 2255AN: 152178Hom.: 19 Cov.: 33 AF XY: 0.0136 AC XY: 1015AN XY: 74412
GnomAD4 genome
AF:
AC:
2255
AN:
152178
Hom.:
Cov.:
33
AF XY:
AC XY:
1015
AN XY:
74412
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
5
AN:
3470
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 29, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at