rs12982178

Variant names:

• chr19-17260759-T-C
• rs12982178
• NM_031941.4:c.643-737A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031941.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USHBP1	NM_031941.4	MANE Select	c.643-737A>G		intron	N/A	NP_114147.2
	USHBP1	NM_001321417.2		c.643-737A>G		intron	N/A	NP_001308346.1	Q8N6Y0-1
	USHBP1	NM_001297703.2		c.451-737A>G		intron	N/A	NP_001284632.1	G8JLM4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USHBP1	ENST00000252597.8	TSL:1 MANE Select	c.643-737A>G		intron	N/A	ENSP00000252597.2	Q8N6Y0-1
	USHBP1	ENST00000881047.1		c.643-737A>G		intron	N/A	ENSP00000551106.1
	USHBP1	ENST00000881048.1		c.643-737A>G		intron	N/A	ENSP00000551107.1

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

African (AFR) AF: 0.145 AC: 6006 AN: 41520

American (AMR) AF: 0.109 AC: 1670 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 643 AN: 3470

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5186

South Asian (SAS) AF: 0.111 AC: 537 AN: 4826

European-Finnish (FIN) AF: 0.241 AC: 2545 AN: 10574

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13595 AN: 67976

Other (OTH) AF: 0.154 AC: 325 AN: 2110

Alfa AF: 0.182 Hom.: 4004

Bravo AF: 0.156

Asia WGS AF: 0.0570 AC: 200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.7
DANN	Benign	0.64
PhyloP100		-0.14
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: rs12982178; hg19: chr19-17371568;