rs12982178

chr19-17260759-T-C

Variant summary

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

The NM_031941.4(USHBP1):c.643-737A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,146 control chromosomes in the GnomAD database, including 2,331 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 0.17 (2331 hom., cov: 32)
• Consequence: USHBP1 NM_031941.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.145

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USHBP1	NM_031941.4	c.643-737A>G		intron_variant		ENST00000252597.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USHBP1	ENST00000252597.8	c.643-737A>G		intron_variant		1	NM_031941.4	P1
USHBP1	ENST00000431146.6	c.451-737A>G		intron_variant		2
USHBP1	ENST00000324554.9	c.643-737A>G		intron_variant, NMD_transcript_variant		2
USHBP1	ENST00000597928.5	c.*1447-737A>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25423 AN: 152028 Hom.: 2332 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.167 AC: 25416 AN: 152146 Hom.: 2331 Cov.: 32 AF XY: 0.165 AC XY: 12236 AN XY: 74362

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.154

Alfa AF: 0.184 Hom.: 2803

Bravo AF: 0.156

Asia WGS AF: 0.0570 AC: 200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	5.7
Dann	Benign	0.64

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: rs12982178; hg19: chr19-17371568;