rs982874

Variant names:

• chr6-51870463-G-T
• rs982874
• NM_138694.4:c.7486+41C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-51870463-G-T
• chr6-51870463-G-A
• chr6-51870463-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_138694.4(PKHD1):​c.7486+41C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 1,505,382 control chromosomes in the GnomAD database, including 106,749 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (13487 hom., cov: 32)
  • Exomes 𝑓: 0.35 (93262 hom.)
• Consequence: PKHD1 NM_138694.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0140
• Publications: 8 publications found

Genes affected

PKHD1 (HGNC:9016): (PKHD1 ciliary IPT domain containing fibrocystin/polyductin) The protein encoded by this gene is predicted to have a single transmembrane (TM)-spanning domain and multiple copies of an immunoglobulin-like plexin-transcription-factor domain. Alternative splicing results in two transcript variants encoding different isoforms. Other alternatively spliced transcripts have been described, but the full length sequences have not been determined. Several of these transcripts are predicted to encode truncated products which lack the TM and may be secreted. Mutations in this gene cause autosomal recessive polycystic kidney disease, also known as polycystic kidney and hepatic disease-1. [provided by RefSeq, Jul 2008]

PKHD1 Gene-Disease associations (from GenCC):

• autosomal recessive polycystic kidney disease

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Myriad Women’s Health, Orphanet
• polycystic kidney disease 4

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• Caroli disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 6-51870463-G-T is Benign according to our data. Variant chr6-51870463-G-T is described in ClinVar as Benign. ClinVar VariationId is 262411.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138694.4. 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
	PKHD1	NM_138694.4	MANE Select	c.7486+41C>A		intron	N/A	NP_619639.3
	PKHD1	NM_170724.3		c.7486+41C>A		intron	N/A	NP_733842.2	P08F94-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKHD1	ENST00000371117.8	TSL:1 MANE Select	c.7486+41C>A		intron	N/A	ENSP00000360158.3	P08F94-1
	PKHD1	ENST00000340994.4	TSL:5	c.7486+41C>A		intron	N/A	ENSP00000341097.4	P08F94-2

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61093 AN: 151838 Hom.: 13478 Cov.: 32

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.369

GnomAD2 exomes AF: 0.444 AC: 110853 AN: 249592 AF XY: 0.435

Gnomad AFR exome AF: 0.432

Gnomad AMR exome AF: 0.653

Gnomad ASJ exome AF: 0.253

Gnomad EAS exome AF: 0.867

Gnomad FIN exome AF: 0.450

Gnomad NFE exome AF: 0.314

Gnomad OTH exome AF: 0.373

GnomAD4 exome AF: 0.350 AC: 473357 AN: 1353426 Hom.: 93262 Cov.: 21 AF XY: 0.354 AC XY: 240464 AN XY: 679634

African (AFR) AF: 0.412 AC: 12883 AN: 31270

American (AMR) AF: 0.633 AC: 28121 AN: 44394

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 6343 AN: 25480

East Asian (EAS) AF: 0.826 AC: 32138 AN: 38890

South Asian (SAS) AF: 0.511 AC: 42702 AN: 83516

European-Finnish (FIN) AF: 0.436 AC: 23186 AN: 53208

Middle Eastern (MID) AF: 0.264 AC: 1466 AN: 5558

European-Non Finnish (NFE) AF: 0.302 AC: 306338 AN: 1014508

Other (OTH) AF: 0.357 AC: 20180 AN: 56602

GnomAD4 genome AF: 0.402 AC: 61132 AN: 151956 Hom.: 13487 Cov.: 32 AF XY: 0.418 AC XY: 31013 AN XY: 74276

African (AFR) AF: 0.431 AC: 17846 AN: 41446

American (AMR) AF: 0.532 AC: 8110 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 902 AN: 3470

East Asian (EAS) AF: 0.851 AC: 4405 AN: 5178

South Asian (SAS) AF: 0.539 AC: 2599 AN: 4822

European-Finnish (FIN) AF: 0.453 AC: 4783 AN: 10548

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21522 AN: 67920

Other (OTH) AF: 0.367 AC: 776 AN: 2114

Alfa AF: 0.320 Hom.: 2913

Bravo AF: 0.407

Asia WGS AF: 0.624 AC: 2167 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Autosomal recessive polycystic kidney disease (1)
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Polycystic kidney disease 4 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.36
DANN	Benign	0.66
PhyloP100		-0.014
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: rs982874; hg19: chr6-51735261;