rs2296553

Positions:

• chr9-37711597-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014907.3(FRMPD1):​c.408+202A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 151,954 control chromosomes in the GnomAD database, including 13,238 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 0.42 (13238 hom., cov: 32)
• Consequence: FRMPD1 NM_014907.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.206

Genes affected

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

Verdict is Benign. Variant got -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 = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMPD1	NM_014907.3	c.408+202A>C		intron_variant		ENST00000377765.8	NP_055722.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRMPD1	ENST00000377765.8	c.408+202A>C		intron_variant		1	NM_014907.3	ENSP00000366995	P1
FRMPD1	ENST00000539465.5	c.408+202A>C		intron_variant		1		ENSP00000444411	P1

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63239 AN: 151836 Hom.: 13227 Cov.: 32

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.416 AC: 63285 AN: 151954 Hom.: 13238 Cov.: 32 AF XY: 0.415 AC XY: 30782 AN XY: 74256

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.564

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.440

Gnomad4 OTH AF: 0.439

Alfa AF: 0.432 Hom.: 19038

Bravo AF: 0.413

Asia WGS AF: 0.430 AC: 1500 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	4.3
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs2296553; hg19: chr9-37711594;