rs6876035

Variant names:

• chr5-32581497-C-T
• rs6876035
• ENST00000506237.5:c.-1-7015C>T

Variant summary

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

The ENST00000506237.5(SUB1):​c.-1-7015C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,086 control chromosomes in the GnomAD database, including 8,856 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 0.33 (8856 hom., cov: 32)
• Consequence: SUB1 ENST00000506237.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.751

Genes affected

SUB1 (HGNC:19985): (SUB1 regulator of transcription) Enables identical protein binding activity; single-stranded DNA binding activity; and transcription coactivator activity. Involved in negative regulation of DNA metabolic process and regulation of transcription by RNA polymerase II. Located in nucleolus and nucleoplasm. Part of transcription regulator complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUB1	ENST00000506237.5	c.-1-7015C>T		intron_variant	Intron 1 of 4	2		ENSP00000422078.1
SUB1	ENST00000512913.5	c.-1-7015C>T		intron_variant	Intron 2 of 5	2		ENSP00000422806.1
SUB1	ENST00000513013.5	n.211-10066C>T		intron_variant	Intron 3 of 5	5

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49729 AN: 151968 Hom.: 8855 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.327 AC: 49737 AN: 152086 Hom.: 8856 Cov.: 32 AF XY: 0.329 AC XY: 24436 AN XY: 74334

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.324

Alfa AF: 0.376 Hom.: 15907

Bravo AF: 0.314

Asia WGS AF: 0.361 AC: 1254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	2.8
DANN	Benign	0.87

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: rs6876035; hg19: chr5-32581603; COSMIC: COSV54083549; COSMIC: COSV54083549;