ENST00000540557.1:n.*1136-46370A>G

Variant names:

• chr9-37635302-T-C
• rs999988
• ENST00000540557.1:n.*1136-46370A>G

Variant summary

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

The ENST00000540557.1(ENSG00000255872):​n.*1136-46370A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 152,056 control chromosomes in the GnomAD database, including 40,614 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 0.72 (40614 hom., cov: 32)
• Consequence: ENSG00000255872 ENST00000540557.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08
• Publications: 3 publications found

Genes affected

ENSG00000255872 (HGNC:):

FRMPD1 (HGNC:29159): (FERM and PDZ domain containing 1) Involved in establishment of protein localization to membrane and regulation of G protein-coupled receptor signaling pathway. Located in plasma membrane. Part of protein-containing complex. Colocalizes with cell cortex. [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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMPD1	NM_001371224.1	c.-5+11982T>C		intron_variant	Intron 2 of 16		NP_001358153.1
FRMPD1	NM_001371225.1	c.-5+31963T>C		intron_variant	Intron 1 of 15		NP_001358154.1
FRMPD1	XM_047423003.1	c.-5+11982T>C		intron_variant	Intron 2 of 16		XP_047278959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000255872	ENST00000540557.1	n.*1136-46370A>G		intron_variant	Intron 11 of 11	5		ENSP00000457548.1

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109399 AN: 151938 Hom.: 40588 Cov.: 32

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.842

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.794

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.743

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

GnomAD4 genome AF: 0.720 AC: 109475 AN: 152056 Hom.: 40614 Cov.: 32 AF XY: 0.720 AC XY: 53470 AN XY: 74306

African (AFR) AF: 0.555 AC: 22990 AN: 41442

American (AMR) AF: 0.760 AC: 11605 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.842 AC: 2923 AN: 3472

East Asian (EAS) AF: 0.419 AC: 2157 AN: 5154

South Asian (SAS) AF: 0.764 AC: 3672 AN: 4808

European-Finnish (FIN) AF: 0.794 AC: 8404 AN: 10582

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.813 AC: 55258 AN: 68008

Other (OTH) AF: 0.747 AC: 1577 AN: 2112

Alfa AF: 0.778 Hom.: 160244

Bravo AF: 0.707

Asia WGS AF: 0.616 AC: 2142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.99
DANN	Benign	0.63
PhyloP100		-2.1

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: rs999988; hg19: chr9-37635299;