NM_138295.5:c.8194-66C>T

Variant names:

• chr7-47796216-G-A
• rs6943728
• NM_138295.5:c.8194-66C>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.8194-66C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 1,326,426 control chromosomes in the GnomAD database, including 157,595 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.44 (15403 hom., cov: 33)
  • Exomes 𝑓: 0.49 (142192 hom.)
• Consequence: PKD1L1 NM_138295.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.731
• Publications: 1 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-AS1 (HGNC:21911): (PKD1L1 antisense RNA 1) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 7-47796216-G-A is Benign according to our data. Variant chr7-47796216-G-A is described in ClinVar as Benign. ClinVar VariationId is 1276259.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.577 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.8194-66C>T		intron	N/A	NP_612152.1	Q8TDX9-1
	PKD1L1-AS1	NR_161268.1		n.153+773G>A		intron	N/A
	PKD1L1-AS1	NR_161269.1		n.153+773G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1L1	ENST00000289672.7	TSL:1 MANE Select	c.8194-66C>T		intron	N/A	ENSP00000289672.2	Q8TDX9-1
	PKD1L1-AS1	ENST00000623971.3	TSL:1	n.153+773G>A		intron	N/A
	PKD1L1	ENST00000690269.1		c.8194-66C>T		intron	N/A	ENSP00000510743.1	A0A8I5KWV8

Frequencies

GnomAD3 genomes AF: 0.441 AC: 66936 AN: 151854 Hom.: 15399 Cov.: 33

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.474

GnomAD4 exome AF: 0.490 AC: 575927 AN: 1174454 Hom.: 142192 AF XY: 0.490 AC XY: 287889 AN XY: 587984

African (AFR) AF: 0.300 AC: 7852 AN: 26138

American (AMR) AF: 0.476 AC: 12651 AN: 26602

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 9273 AN: 20204

East Asian (EAS) AF: 0.590 AC: 22319 AN: 37804

South Asian (SAS) AF: 0.434 AC: 28602 AN: 65868

European-Finnish (FIN) AF: 0.412 AC: 17503 AN: 42468

Middle Eastern (MID) AF: 0.484 AC: 1806 AN: 3734

European-Non Finnish (NFE) AF: 0.501 AC: 451669 AN: 901332

Other (OTH) AF: 0.482 AC: 24252 AN: 50304

GnomAD4 genome AF: 0.440 AC: 66943 AN: 151972 Hom.: 15403 Cov.: 33 AF XY: 0.438 AC XY: 32515 AN XY: 74284

African (AFR) AF: 0.312 AC: 12947 AN: 41450

American (AMR) AF: 0.506 AC: 7738 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1602 AN: 3468

East Asian (EAS) AF: 0.595 AC: 3071 AN: 5162

South Asian (SAS) AF: 0.434 AC: 2090 AN: 4814

European-Finnish (FIN) AF: 0.409 AC: 4304 AN: 10514

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33708 AN: 67960

Other (OTH) AF: 0.478 AC: 1009 AN: 2112

Alfa AF: 0.456 Hom.: 3167

Bravo AF: 0.440

Asia WGS AF: 0.492 AC: 1709 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	-0.93
CADD	Benign	0.46
DANN	Benign	0.66
PhyloP100		-0.73
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: rs6943728; hg19: chr7-47835814; COSMIC: COSV51842711;