rs6876035

Variant names:

• chr5-32581497-C-T
• rs6876035
• ENST00000506237.6:c.-1-7015C>T

Variant summary

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

The ENST00000506237.6(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 ENST00000506237.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.751
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000506237.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUB1	ENST00000506237.6	TSL:2	c.-1-7015C>T		intron	N/A	ENSP00000422078.1	P53999
	SUB1	ENST00000512913.5	TSL:2	c.-1-7015C>T		intron	N/A	ENSP00000422806.1	P53999
	SUB1	ENST00000879054.1		c.-1-7015C>T		intron	N/A	ENSP00000549113.1

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

African (AFR) AF: 0.177 AC: 7345 AN: 41500

American (AMR) AF: 0.359 AC: 5488 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1203 AN: 3470

East Asian (EAS) AF: 0.359 AC: 1855 AN: 5160

South Asian (SAS) AF: 0.409 AC: 1972 AN: 4820

European-Finnish (FIN) AF: 0.418 AC: 4423 AN: 10584

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.387 AC: 26282 AN: 67944

Other (OTH) AF: 0.324 AC: 685 AN: 2114

Alfa AF: 0.362 Hom.: 24705

Bravo AF: 0.314

Asia WGS AF: 0.361 AC: 1254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	2.8
DANN	Benign	0.87
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6876035;

hg19: chr5-32581603;

COSMIC: COSV54083549;

COSMIC: COSV54083549;