2-113182186-T-A

Variant names:

• chr2-113182186-T-A
• rs4849166
• NM_012455.3:c.-111-160T>A

Variant summary

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

The NM_012455.3(PSD4):​c.-111-160T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 152,002 control chromosomes in the GnomAD database, including 18,596 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 0.49 (18596 hom., cov: 32)
• Consequence: PSD4 NM_012455.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.47
• Publications: 5 publications found

Genes affected

PSD4 (HGNC:19096): (pleckstrin and Sec7 domain containing 4) Predicted to enable guanyl-nucleotide exchange factor activity and phospholipid binding activity. Predicted to be involved in regulation of ARF protein signal transduction and regulation of catalytic activity. Located in ruffle membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012455.3. 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
	PSD4	NM_012455.3	MANE Select	c.-111-160T>A		intron	N/A	NP_036587.2	Q8NDX1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSD4	ENST00000245796.11	TSL:1 MANE Select	c.-111-160T>A		intron	N/A	ENSP00000245796.6	Q8NDX1-1
	PSD4	ENST00000441564.7	TSL:1	c.-111-160T>A		intron	N/A	ENSP00000413997.2	Q8NDX1-2
	PSD4	ENST00000893514.1		c.-111-160T>A		intron	N/A	ENSP00000563573.1

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74123 AN: 151882 Hom.: 18559 Cov.: 32

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.616

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.477

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.488 AC: 74216 AN: 152002 Hom.: 18596 Cov.: 32 AF XY: 0.493 AC XY: 36620 AN XY: 74304

African (AFR) AF: 0.593 AC: 24584 AN: 41452

American (AMR) AF: 0.473 AC: 7228 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1359 AN: 3466

East Asian (EAS) AF: 0.615 AC: 3180 AN: 5168

South Asian (SAS) AF: 0.505 AC: 2437 AN: 4826

European-Finnish (FIN) AF: 0.568 AC: 6007 AN: 10570

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.412 AC: 27960 AN: 67936

Other (OTH) AF: 0.480 AC: 1012 AN: 2108

Alfa AF: 0.270 Hom.: 660

Bravo AF: 0.487

Asia WGS AF: 0.589 AC: 2045 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0040
DANN	Benign	0.34
PhyloP100		-4.5
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: rs4849166; hg19: chr2-113939763;