rs6876035

Positions:

• chr5-32581497-C-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/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUB1	ENST00000506237.5	c.-1-7015C>T		intron_variant		2		ENSP00000422078	P1
SUB1	ENST00000512913.5	c.-1-7015C>T		intron_variant		2		ENSP00000422806	P1
SUB1	ENST00000513013.5	n.211-10066C>T		intron_variant, non_coding_transcript_variant		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;