rs16853272

Positions:

• chr1-204311708-T-C
• chr1-204311708-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_014935.5(PLEKHA6):​c.-94-36899A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.022 in 931,728 control chromosomes in the GnomAD database, including 257 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 0.022 (42 hom., cov: 32)
  • Exomes 𝑓: 0.022 (215 hom.)
• Consequence: PLEKHA6 NM_014935.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.575

Genes affected

PLEKHA6 (HGNC:17053): (pleckstrin homology domain containing A6)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0224 (3412/152356) while in subpopulation SAS AF= 0.0304 (147/4830). AF 95% confidence interval is 0.0264. There are 42 homozygotes in gnomad4. There are 1603 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 42 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHA6	NM_014935.5	c.-94-36899A>G		intron_variant		ENST00000272203.8	NP_055750.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLEKHA6	ENST00000272203.8	c.-94-36899A>G		intron_variant		1	NM_014935.5	ENSP00000272203.2
PLEKHA6	ENST00000414478.1	c.-94-36899A>G		intron_variant		5		ENSP00000402046.1
PLEKHA6	ENST00000564627.2	c.219-36899A>G		intron_variant		3		ENSP00000490720.2

Frequencies

GnomAD3 genomes AF: 0.0224 AC: 3410 AN: 152238 Hom.: 41 Cov.: 32

Gnomad AFR AF: 0.0234

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0223

Gnomad ASJ AF: 0.0372

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0304

Gnomad FIN AF: 0.00828

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0240

Gnomad OTH AF: 0.0296

GnomAD4 exome AF: 0.0219 AC: 17054 AN: 779372 Hom.: 215 Cov.: 12 AF XY: 0.0217 AC XY: 7841 AN XY: 361190

Gnomad4 AFR exome AF: 0.0231

Gnomad4 AMR exome AF: 0.0142

Gnomad4 ASJ exome AF: 0.0393

Gnomad4 EAS exome AF: 0.000293

Gnomad4 SAS exome AF: 0.0271

Gnomad4 FIN exome AF: 0.0276

Gnomad4 NFE exome AF: 0.0217

Gnomad4 OTH exome AF: 0.0227

GnomAD4 genome AF: 0.0224 AC: 3412 AN: 152356 Hom.: 42 Cov.: 32 AF XY: 0.0215 AC XY: 1603 AN XY: 74504

Gnomad4 AFR AF: 0.0234

Gnomad4 AMR AF: 0.0222

Gnomad4 ASJ AF: 0.0372

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0304

Gnomad4 FIN AF: 0.00828

Gnomad4 NFE AF: 0.0240

Gnomad4 OTH AF: 0.0289

Alfa AF: 0.00488 Hom.: 1

Bravo AF: 0.0229

Asia WGS AF: 0.0120 AC: 41 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	17
DANN	Benign	0.85

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

Publications

LitVar

Other links and lift over

dbSNP: rs16853272; hg19: chr1-204280836;