rs4808075

chr19-17279482-T-C

Variant summary

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

The ENST00000598309.1(USHBP1):c.-201+3054A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 161,458 control chromosomes in the GnomAD database, including 5,383 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 0.25 (5089 hom., cov: 31)
  • Exomes 𝑓: 0.22 (294 hom.)
• Consequence: USHBP1 ENST00000598309.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

Genes affected

USHBP1 (HGNC:24058): (USH1 protein network component harmonin binding protein 1) Enables PDZ domain binding activity. [provided by Alliance of Genome Resources, Apr 2022]

BABAM1 (HGNC:25008): (BRISC and BRCA1 A complex member 1) Involved in several processes, including mitotic G2 DNA damage checkpoint signaling; positive regulation of DNA repair; and protein K63-linked deubiquitination. Located in cytosol and nuclear body. Part of BRCA1-A complex and BRISC 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.292 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
USHBP1	ENST00000598309.1	c.-201+3054A>G		intron_variant		4
BABAM1	ENST00000594247.5	c.*499-1754T>C		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37960 AN: 151880 Hom.: 5086 Cov.: 31

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.250

GnomAD4 exome AF: 0.219 AC: 2073 AN: 9460 Hom.: 294 AF XY: 0.220 AC XY: 1058 AN XY: 4808

Gnomad4 AFR exome AF: 0.223

Gnomad4 AMR exome AF: 0.112

Gnomad4 ASJ exome AF: 0.287

Gnomad4 EAS exome AF: 0.00202

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.290

Gnomad4 NFE exome AF: 0.246

Gnomad4 OTH exome AF: 0.198

GnomAD4 genome AF: 0.250 AC: 37968 AN: 151998 Hom.: 5089 Cov.: 31 AF XY: 0.245 AC XY: 18208 AN XY: 74284

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.275

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.315

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.249

Alfa AF: 0.201 Hom.: 774

Bravo AF: 0.238

Asia WGS AF: 0.0830 AC: 291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.80
Dann	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4808075; hg19: chr19-17390291;