5-32584479-G-C

Variant summary

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

The ENST00000506237.5(SUB1):c.-1-4033G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 143,318 control chromosomes in the GnomAD database, including 8,814 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 0.35 (8814 hom., cov: 28)
• Consequence: SUB1 ENST00000506237.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.767

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUB1	ENST00000506237.5	c.-1-4033G>C		intron_variant		2		P1
SUB1	ENST00000512913.5	c.-1-4033G>C		intron_variant		2		P1
SUB1	ENST00000513013.5	n.211-7084G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.346 AC: 49494 AN: 143240 Hom.: 8813 Cov.: 28

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.342

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

GnomAD4 genome AF: 0.345 AC: 49501 AN: 143318 Hom.: 8814 Cov.: 28 AF XY: 0.350 AC XY: 24286 AN XY: 69396

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.385

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.468

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.340

Alfa AF: 0.246 Hom.: 682

Bravo AF: 0.314

Asia WGS AF: 0.360 AC: 1253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.098
Dann	Benign	0.39

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: rs2008245; hg19: chr5-32584585;