NM_177531.6:c.11554-1796A>G

Variant names:

• chr8-109513374-A-G
• rs6469264
• NM_177531.6:c.11554-1796A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

PKHD1L1 Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 124

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177531.6. 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
	PKHD1L1	NM_177531.6	MANE Select	c.11554-1796A>G		intron	N/A	NP_803875.2	Q86WI1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKHD1L1	ENST00000378402.10	TSL:1 MANE Select	c.11554-1796A>G		intron	N/A	ENSP00000367655.5	Q86WI1
	PKHD1L1	ENST00000526472.1	TSL:2	c.2338-1796A>G		intron	N/A	ENSP00000437376.1	H0YF65

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

African (AFR) AF: 0.144 AC: 5960 AN: 41506

American (AMR) AF: 0.140 AC: 2140 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 748 AN: 3466

East Asian (EAS) AF: 0.00328 AC: 17 AN: 5182

South Asian (SAS) AF: 0.367 AC: 1771 AN: 4820

European-Finnish (FIN) AF: 0.192 AC: 2029 AN: 10580

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13961 AN: 67968

Other (OTH) AF: 0.197 AC: 416 AN: 2110

Alfa AF: 0.181 Hom.: 448

Bravo AF: 0.168

Asia WGS AF: 0.214 AC: 746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.86
PhyloP100		0.26
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: rs6469264; hg19: chr8-110525603;