4-94584441-A-T

Variant names:

• chr4-94584441-A-T
• rs7682375
• ENST00000380176.7:n.41A>T

Variant summary

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

The ENST00000380176.7(PDLIM5):​n.41A>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,124 control chromosomes in the GnomAD database, including 5,395 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 0.25 (5395 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: PDLIM5 ENST00000380176.7 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201
• Publications: 6 publications found

Genes affected

PDLIM5 (HGNC:17468): (PDZ and LIM domain 5) This gene encodes a member of a family of proteins that possess a 100-amino acid PDZ domain at the N terminus and one to three LIM domains at the C-terminus. This family member functions as a scaffold protein that tethers protein kinases to the Z-disk in striated muscles. It is thought to function in cardiomyocyte expansion and in restraining postsynaptic growth of excitatory synapses. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2012]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDLIM5	NM_006457.5	c.711-1124A>T		intron_variant	Intron 5 of 12	ENST00000317968.9	NP_006448.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDLIM5	ENST00000317968.9	c.711-1124A>T		intron_variant	Intron 5 of 12	1	NM_006457.5	ENSP00000321746.4

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38333 AN: 151974 Hom.: 5393 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.277

GnomAD4 exome AF: 0.250 AC: 8 AN: 32 Hom.: 0 Cov.: 0 AF XY: 0.417 AC XY: 5 AN XY: 12

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

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.200 AC: 4 AN: 20

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.252 AC: 38335 AN: 152092 Hom.: 5395 Cov.: 32 AF XY: 0.251 AC XY: 18688 AN XY: 74352

African (AFR) AF: 0.129 AC: 5347 AN: 41508

American (AMR) AF: 0.266 AC: 4063 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1012 AN: 3470

East Asian (EAS) AF: 0.380 AC: 1965 AN: 5170

South Asian (SAS) AF: 0.135 AC: 651 AN: 4824

European-Finnish (FIN) AF: 0.280 AC: 2958 AN: 10564

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21480 AN: 67956

Other (OTH) AF: 0.274 AC: 580 AN: 2114

Alfa AF: 0.157 Hom.: 352

Bravo AF: 0.246

Asia WGS AF: 0.213 AC: 743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.70
DANN	Benign	0.78
PhyloP100		-0.20
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: rs7682375; hg19: chr4-95505592;