14-69500567-T-C

Position:

• chr14-69500567-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001161498.2(PLEKHD1):​c.244-10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00299 in 1,544,800 control chromosomes in the GnomAD database, including 127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (64 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (63 hom.)
• Consequence: PLEKHD1 NM_001161498.2 intron
• Scores: Splicing: ADA: 0.03670
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.92

Genes affected

PLEKHD1 (HGNC:20148): (pleckstrin homology and coiled-coil domain containing D1)

PLEKHD1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 14-69500567-T-C is Benign according to our data. Variant chr14-69500567-T-C is described in ClinVar as [Benign]. Clinvar id is 785462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHD1	NM_001161498.2	c.244-10T>C		intron_variant		ENST00000322564.9	NP_001154970.1
PLEKHD1	XM_017021290.1	c.-51-10T>C		intron_variant			XP_016876779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLEKHD1	ENST00000322564.9	c.244-10T>C		intron_variant		1	NM_001161498.2	ENSP00000317175.7
PLEKHD1	ENST00000556123.1	n.876T>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.0158 AC: 2400 AN: 152128 Hom.: 64 Cov.: 33

Gnomad AFR AF: 0.0546

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00517

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000324

Gnomad OTH AF: 0.0167

GnomAD3 exomes AF: 0.00416 AC: 616 AN: 147910 Hom.: 22 AF XY: 0.00341 AC XY: 267 AN XY: 78290

Gnomad AFR exome AF: 0.0638

Gnomad AMR exome AF: 0.00373

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000138

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000264

Gnomad OTH exome AF: 0.00193

GnomAD4 exome AF: 0.00159 AC: 2210 AN: 1392554 Hom.: 63 Cov.: 31 AF XY: 0.00144 AC XY: 991 AN XY: 686472

Gnomad4 AFR exome AF: 0.0553

Gnomad4 AMR exome AF: 0.00407

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000107

Gnomad4 OTH exome AF: 0.00336

GnomAD4 genome AF: 0.0158 AC: 2407 AN: 152246 Hom.: 64 Cov.: 33 AF XY: 0.0155 AC XY: 1152 AN XY: 74448

Gnomad4 AFR AF: 0.0546

Gnomad4 AMR AF: 0.00516

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000324

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.0122 Hom.: 16

Bravo AF: 0.0185

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 18, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	17
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.037
dbscSNV1_RF	Benign	0.28
SpliceAI score (max)		0.010		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: rs143684449; hg19: chr14-69967284;