chr5-32575808-G-A

Variant names:

• chr5-32575808-G-A
• rs7726475
• ENST00000506237.6:c.-1-12704G>A

Variant summary

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

The ENST00000506237.6(SUB1):​c.-1-12704G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,158 control chromosomes in the GnomAD database, including 5,679 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 0.24 (5679 hom., cov: 33)
• Consequence: SUB1 ENST00000506237.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.349
• Publications: 11 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.326 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUB1	ENST00000506237.6	TSL:2	c.-1-12704G>A		intron	N/A	ENSP00000422078.1
	SUB1	ENST00000512913.5	TSL:2	c.-2+4634G>A		intron	N/A	ENSP00000422806.1
	SUB1	ENST00000513013.5	TSL:5	n.210+4634G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37254 AN: 152040 Hom.: 5676 Cov.: 33

Gnomad AFR AF: 0.0686

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.245 AC: 37248 AN: 152158 Hom.: 5679 Cov.: 33 AF XY: 0.246 AC XY: 18313 AN XY: 74376

African (AFR) AF: 0.0684 AC: 2841 AN: 41544

American (AMR) AF: 0.274 AC: 4184 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1121 AN: 3470

East Asian (EAS) AF: 0.108 AC: 560 AN: 5176

South Asian (SAS) AF: 0.275 AC: 1322 AN: 4812

European-Finnish (FIN) AF: 0.361 AC: 3805 AN: 10554

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22393 AN: 68004

Other (OTH) AF: 0.265 AC: 559 AN: 2112

Alfa AF: 0.272 Hom.: 3041

Bravo AF: 0.229

Asia WGS AF: 0.198 AC: 690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.60
PhyloP100		-0.35
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

Other links and lift over

dbSNP: rs7726475; hg19: chr5-32575914;