NM_001001974.4:c.811-91G>A

Variant names:

• chr10-122426851-G-A
• rs2292625
• NM_001001974.4:c.811-91G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001001974.4(PLEKHA1):​c.811-91G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 1,117,128 control chromosomes in the GnomAD database, including 15,229 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 0.15 (1775 hom., cov: 32)
  • Exomes 𝑓: 0.16 (13454 hom.)
• Consequence: PLEKHA1 NM_001001974.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.418
• Publications: 5 publications found

Genes affected

PLEKHA1 (HGNC:14335): (pleckstrin homology domain containing A1) This gene encodes a pleckstrin homology domain-containing adapter protein. The encoded protein is localized to the plasma membrane where it specifically binds phosphatidylinositol 3,4-bisphosphate. This protein may be involved in the formation of signaling complexes in the plasma membrane. Polymorphisms in this gene are associated with age-related macular degeneration. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 5.[provided by RefSeq, Sep 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001974.4. 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
	PLEKHA1	NM_001001974.4	MANE Select	c.811-91G>A		intron	N/A	NP_001001974.1	Q9HB21-1
	PLEKHA1	NM_001377230.1		c.811-91G>A		intron	N/A	NP_001364159.1	Q9HB21-1
	PLEKHA1	NM_001377231.1		c.811-91G>A		intron	N/A	NP_001364160.1	Q9HB21-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHA1	ENST00000368990.8	TSL:1 MANE Select	c.811-91G>A		intron	N/A	ENSP00000357986.3	Q9HB21-1
	PLEKHA1	ENST00000392799.7	TSL:1	c.811-91G>A		intron	N/A	ENSP00000376547.3	Q9HB21-1
	PLEKHA1	ENST00000433307.2	TSL:1	c.811-91G>A		intron	N/A	ENSP00000394416.1	Q9HB21-1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22252 AN: 152078 Hom.: 1773 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.0585

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.0829

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.162

GnomAD4 exome AF: 0.162 AC: 156340 AN: 964932 Hom.: 13454 AF XY: 0.162 AC XY: 79104 AN XY: 487768

African (AFR) AF: 0.138 AC: 3008 AN: 21826

American (AMR) AF: 0.0913 AC: 2498 AN: 27348

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 4765 AN: 19758

East Asian (EAS) AF: 0.0515 AC: 1787 AN: 34692

South Asian (SAS) AF: 0.154 AC: 9900 AN: 64194

European-Finnish (FIN) AF: 0.0825 AC: 3731 AN: 45240

Middle Eastern (MID) AF: 0.216 AC: 775 AN: 3592

European-Non Finnish (NFE) AF: 0.174 AC: 122841 AN: 705122

Other (OTH) AF: 0.163 AC: 7035 AN: 43160

GnomAD4 genome AF: 0.146 AC: 22254 AN: 152196 Hom.: 1775 Cov.: 32 AF XY: 0.140 AC XY: 10451 AN XY: 74434

African (AFR) AF: 0.139 AC: 5767 AN: 41514

American (AMR) AF: 0.121 AC: 1854 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 822 AN: 3470

East Asian (EAS) AF: 0.0586 AC: 304 AN: 5188

South Asian (SAS) AF: 0.149 AC: 717 AN: 4824

European-Finnish (FIN) AF: 0.0829 AC: 879 AN: 10598

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11388 AN: 67988

Other (OTH) AF: 0.160 AC: 338 AN: 2112

Alfa AF: 0.151 Hom.: 287

Bravo AF: 0.150

Asia WGS AF: 0.0890 AC: 311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.61
DANN	Benign	0.32
PhyloP100		-0.42
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: rs2292625; hg19: chr10-124186367;