chr5-32604515-G-C

Variant names:

• chr5-32604515-G-C
• rs11744644
• ENST00000506237.6:c.*3431G>C

Variant summary

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

The ENST00000506237.6(SUB1):​c.*3431G>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 151,964 control chromosomes in the GnomAD database, including 6,804 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 0.27 (6804 hom., cov: 32)
• Consequence: SUB1 ENST00000506237.6 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.538
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.361 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	ENST00000506237.6	c.*3431G>C		downstream_gene_variant		2		ENSP00000422078.1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40697 AN: 151846 Hom.: 6800 Cov.: 32

Gnomad AFR AF: 0.0748

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.268 AC: 40693 AN: 151964 Hom.: 6804 Cov.: 32 AF XY: 0.269 AC XY: 19997 AN XY: 74258

African (AFR) AF: 0.0746 AC: 3091 AN: 41454

American (AMR) AF: 0.285 AC: 4356 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1139 AN: 3464

East Asian (EAS) AF: 0.110 AC: 572 AN: 5182

South Asian (SAS) AF: 0.294 AC: 1416 AN: 4818

European-Finnish (FIN) AF: 0.408 AC: 4294 AN: 10524

Middle Eastern (MID) AF: 0.288 AC: 84 AN: 292

European-Non Finnish (NFE) AF: 0.365 AC: 24767 AN: 67930

Other (OTH) AF: 0.273 AC: 576 AN: 2108

Alfa AF: 0.303 Hom.: 958

Bravo AF: 0.248

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.41
DANN	Benign	0.69
PhyloP100		-0.54

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11744644; hg19: chr5-32604621;