rs17545279

Variant names:

• chr7-47774931-G-A
• rs17545279
• NM_138295.5:c.*212C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_138295.5(PKD1L1):​c.*212C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 585,100 control chromosomes in the GnomAD database, including 6,243 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1457 hom., cov: 33)
  • Exomes 𝑓: 0.14 (4786 hom.)
• Consequence: PKD1L1 NM_138295.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.45
• Publications: 4 publications found

Genes affected

PKD1L1 (HGNC:18053): (polycystin 1 like 1, transient receptor potential channel interacting) This gene encodes a member of the polycystin protein family containing 11 transmembrane domains, a receptor for egg jelly (REJ) domain, and a polycystin-1, lipoxygenase, alpha-toxin (PLAT) domain. The encoded protein may play a role in the male reproductive system. Alternative splice variants have been described but their biological nature has not been determined. [provided by RefSeq, Jul 2008]

PKD1L1 Gene-Disease associations (from GenCC):

• heterotaxy, visceral, 8, autosomal

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• situs inversus

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 7-47774931-G-A is Benign according to our data. Variant chr7-47774931-G-A is described in ClinVar as Benign. ClinVar VariationId is 1179665.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138295.5. 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
	PKD1L1	NM_138295.5	MANE Select	c.*212C>T		3_prime_UTR	Exon 57 of 57	NP_612152.1	Q8TDX9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1L1	ENST00000289672.7	TSL:1 MANE Select	c.*212C>T		3_prime_UTR	Exon 57 of 57	ENSP00000289672.2	Q8TDX9-1
	PKD1L1	ENST00000690269.1		c.*212C>T		3_prime_UTR	Exon 58 of 58	ENSP00000510743.1	A0A8I5KWV8
	PKD1L1	ENST00000685709.1		c.*212C>T		3_prime_UTR	Exon 56 of 56	ENSP00000509540.1	A0A8I5QKU1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19664 AN: 152048 Hom.: 1454 Cov.: 33

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.0997

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.121

GnomAD4 exome AF: 0.137 AC: 59478 AN: 432934 Hom.: 4786 Cov.: 5 AF XY: 0.138 AC XY: 31586 AN XY: 229678

African (AFR) AF: 0.107 AC: 1298 AN: 12166

American (AMR) AF: 0.0861 AC: 1422 AN: 16524

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 1672 AN: 12422

East Asian (EAS) AF: 0.0264 AC: 794 AN: 30074

South Asian (SAS) AF: 0.131 AC: 5404 AN: 41244

European-Finnish (FIN) AF: 0.252 AC: 8880 AN: 35278

Middle Eastern (MID) AF: 0.117 AC: 389 AN: 3318

European-Non Finnish (NFE) AF: 0.141 AC: 36245 AN: 257562

Other (OTH) AF: 0.139 AC: 3374 AN: 24346

GnomAD4 genome AF: 0.129 AC: 19684 AN: 152166 Hom.: 1457 Cov.: 33 AF XY: 0.135 AC XY: 10029 AN XY: 74388

African (AFR) AF: 0.104 AC: 4313 AN: 41522

American (AMR) AF: 0.0998 AC: 1525 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 435 AN: 3470

East Asian (EAS) AF: 0.0108 AC: 56 AN: 5186

South Asian (SAS) AF: 0.127 AC: 614 AN: 4820

European-Finnish (FIN) AF: 0.260 AC: 2747 AN: 10566

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9547 AN: 68000

Other (OTH) AF: 0.119 AC: 251 AN: 2112

Alfa AF: 0.131 Hom.: 2740

Bravo AF: 0.115

Asia WGS AF: 0.0600 AC: 208 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.2
DANN	Benign	0.55
PhyloP100		1.5
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: rs17545279; hg19: chr7-47814529;