rs6469264

chr8-109513374-A-G

Variant summary

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

The NM_177531.6(PKHD1L1):c.11554-1796A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,096 control chromosomes in the GnomAD database, including 2,613 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 0.18 (2613 hom., cov: 31)
• Consequence: PKHD1L1 NM_177531.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.259

Genes affected

PKHD1L1 (HGNC:20313): (PKHD1 like 1) Predicted to act upstream of or within sensory perception of sound. Predicted to be located in cytosol. [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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKHD1L1	NM_177531.6	c.11554-1796A>G		intron_variant		ENST00000378402.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKHD1L1	ENST00000378402.10	c.11554-1796A>G		intron_variant		1	NM_177531.6	P1
PKHD1L1	ENST00000526472.1	c.2338-1796A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27228 AN: 151978 Hom.: 2606 Cov.: 31

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.179 AC: 27260 AN: 152096 Hom.: 2613 Cov.: 31 AF XY: 0.179 AC XY: 13339 AN XY: 74348

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.00328

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.197

Alfa AF: 0.183 Hom.: 443

Bravo AF: 0.168

Asia WGS AF: 0.214 AC: 746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	12
Dann	Benign	0.86

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: rs6469264; hg19: chr8-110525603;