chr15-75426328-G-T

Variant names:

• chr15-75426328-G-T
• rs8028182
• NM_001145358.2:c.190-3505C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145358.2(SIN3A):​c.190-3505C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 152,014 control chromosomes in the GnomAD database, including 8,600 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 0.30 (8600 hom., cov: 32)
• Consequence: SIN3A NM_001145358.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17
• Publications: 36 publications found

Genes affected

SIN3A (HGNC:19353): (SIN3 transcription regulator family member A) The protein encoded by this gene is a transcriptional regulatory protein. It contains paired amphipathic helix (PAH) domains, which are important for protein-protein interactions and may mediate repression by the Mad-Max complex. [provided by RefSeq, Jul 2008]

SIN3A Gene-Disease associations (from GenCC):

• SIN3A-related intellectual disability syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Illumina, G2P, ClinGen
• chromosome 15q24 deletion syndrome

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• SIN3A-related intellectual disability syndrome due to a point mutation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• congenital diaphragmatic hernia

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIN3A	NM_001145358.2	c.190-3505C>A		intron_variant	Intron 2 of 20	ENST00000394947.8	NP_001138830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIN3A	ENST00000394947.8	c.190-3505C>A		intron_variant	Intron 2 of 20	1	NM_001145358.2	ENSP00000378402.3

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46016 AN: 151896 Hom.: 8571 Cov.: 32

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.305

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.303 AC: 46103 AN: 152014 Hom.: 8600 Cov.: 32 AF XY: 0.304 AC XY: 22566 AN XY: 74290

African (AFR) AF: 0.524 AC: 21708 AN: 41422

American (AMR) AF: 0.248 AC: 3791 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1097 AN: 3468

East Asian (EAS) AF: 0.193 AC: 1000 AN: 5176

South Asian (SAS) AF: 0.352 AC: 1698 AN: 4824

European-Finnish (FIN) AF: 0.189 AC: 1996 AN: 10570

Middle Eastern (MID) AF: 0.318 AC: 93 AN: 292

European-Non Finnish (NFE) AF: 0.203 AC: 13790 AN: 67986

Other (OTH) AF: 0.314 AC: 661 AN: 2108

Alfa AF: 0.229 Hom.: 20719

Bravo AF: 0.313

Asia WGS AF: 0.295 AC: 1022 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	12
DANN	Benign	0.62
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8028182; hg19: chr15-75718669;