10-122442149-T-G

Variant names:

• chr10-122442149-T-G
• rs2292627
• NM_001377230.1:c.*12211T>G

Variant summary

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

The NM_021622.5(PLEKHA1):​c.*12211T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,280 control chromosomes in the GnomAD database, including 1,498 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 0.12 (1496 hom., cov: 32)
  • Exomes 𝑓: 0.19 (2 hom.)
• Consequence: PLEKHA1 NM_021622.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86
• Publications: 15 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]

HTRA1-AS1 (HGNC:58122):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021622.5. 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
	PLEKHA1	NM_001377230.1		c.*12211T>G		3_prime_UTR	Exon 13 of 13	NP_001364159.1	Q9HB21-1
	PLEKHA1	NM_001377231.1		c.*12211T>G		3_prime_UTR	Exon 15 of 15	NP_001364160.1	Q9HB21-1
	PLEKHA1	NM_001377232.1		c.*12211T>G		3_prime_UTR	Exon 14 of 14	NP_001364161.1	Q9HB21-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTRA1-AS1	ENST00000650300.1		n.1853-5517A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17603 AN: 152120 Hom.: 1491 Cov.: 32

Gnomad AFR AF: 0.0244

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.118

GnomAD4 exome AF: 0.190 AC: 8 AN: 42 Hom.: 2 Cov.: 0 AF XY: 0.184 AC XY: 7 AN XY: 38

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.235 AC: 8 AN: 34

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.116 AC: 17616 AN: 152238 Hom.: 1496 Cov.: 32 AF XY: 0.121 AC XY: 9026 AN XY: 74420

African (AFR) AF: 0.0244 AC: 1013 AN: 41562

American (AMR) AF: 0.155 AC: 2375 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 381 AN: 3472

East Asian (EAS) AF: 0.358 AC: 1848 AN: 5162

South Asian (SAS) AF: 0.231 AC: 1113 AN: 4828

European-Finnish (FIN) AF: 0.176 AC: 1867 AN: 10588

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8498 AN: 68014

Other (OTH) AF: 0.116 AC: 245 AN: 2112

Alfa AF: 0.123 Hom.: 2585

Bravo AF: 0.112

Asia WGS AF: 0.273 AC: 946 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.41
DANN	Benign	0.42
PhyloP100		-1.9

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: rs2292627; hg19: chr10-124201665;