15-75374205-A-T

Position:

• chr15-75374205-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145358.2(SIN3A):​c.3591+1460T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 152,078 control chromosomes in the GnomAD database, including 35,079 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 0.67 (35079 hom., cov: 32)
• Consequence: SIN3A NM_001145358.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.51

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIN3A	NM_001145358.2	c.3591+1460T>A		intron_variant		ENST00000394947.8	NP_001138830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIN3A	ENST00000394947.8	c.3591+1460T>A		intron_variant		1	NM_001145358.2	ENSP00000378402	P4

Frequencies

GnomAD3 genomes AF: 0.671 AC: 101937 AN: 151960 Hom.: 35068 Cov.: 32

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.710

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.799

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.741

Gnomad OTH AF: 0.650

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

GnomAD4 genome AF: 0.671 AC: 101979 AN: 152078 Hom.: 35079 Cov.: 32 AF XY: 0.671 AC XY: 49893 AN XY: 74336

Gnomad4 AFR AF: 0.524

Gnomad4 AMR AF: 0.710

Gnomad4 ASJ AF: 0.616

Gnomad4 EAS AF: 0.652

Gnomad4 SAS AF: 0.611

Gnomad4 FIN AF: 0.799

Gnomad4 NFE AF: 0.741

Gnomad4 OTH AF: 0.641

Alfa AF: 0.706 Hom.: 4563

Bravo AF: 0.661

Asia WGS AF: 0.616 AC: 2148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.56
DANN	Benign	0.65

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

Other links and lift over

dbSNP: rs10220738; hg19: chr15-75666546;