rs10472812

Positions:

• chr5-32592068-T-C

Variant summary

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

The NM_006713.4(SUB1):​c.195+383T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,128 control chromosomes in the GnomAD database, including 8,823 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 (8823 hom., cov: 32)
• Consequence: SUB1 NM_006713.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243

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=-0.85).
• 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
SUB1	NM_006713.4	c.195+383T>C		intron_variant		ENST00000265073.9	NP_006704.3
SUB1	XM_011513944.4	c.195+383T>C		intron_variant			XP_011512246.1
SUB1	XM_047416661.1	c.195+383T>C		intron_variant			XP_047272617.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUB1	ENST00000265073.9	c.195+383T>C		intron_variant		1	NM_006713.4	ENSP00000265073	P1

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49628 AN: 152010 Hom.: 8822 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.301

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: 0.326 AC: 49636 AN: 152128 Hom.: 8823 Cov.: 32 AF XY: 0.328 AC XY: 24400 AN XY: 74360

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.337

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.323

Alfa AF: 0.351 Hom.: 3295

Bravo AF: 0.313

Asia WGS AF: 0.362 AC: 1258 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.8
DANN	Benign	0.63

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: rs10472812; hg19: chr5-32592174;