rs750693

Positions:

• chr9-37733928-T-C

Variant summary

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

The NM_014907.3(FRMPD1):​c.1218+103T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 735,630 control chromosomes in the GnomAD database, including 35,951 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 (5587 hom., cov: 32)
  • Exomes 𝑓: 0.31 (30364 hom.)
• Consequence: FRMPD1 NM_014907.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850

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=-0.65).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMPD1	NM_014907.3	c.1218+103T>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.1218+103T>C		intron_variant		1	NM_014907.3	ENSP00000366995	P1
FRMPD1	ENST00000539465.5	c.1218+103T>C		intron_variant		1		ENSP00000444411	P1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37727 AN: 152050 Hom.: 5576 Cov.: 32

Gnomad AFR AF: 0.0930

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.250

GnomAD4 exome AF: 0.314 AC: 183137 AN: 583462 Hom.: 30364 AF XY: 0.320 AC XY: 101168 AN XY: 316102

Gnomad4 AFR exome AF: 0.0970

Gnomad4 AMR exome AF: 0.363

Gnomad4 ASJ exome AF: 0.187

Gnomad4 EAS exome AF: 0.424

Gnomad4 SAS exome AF: 0.450

Gnomad4 FIN exome AF: 0.337

Gnomad4 NFE exome AF: 0.290

Gnomad4 OTH exome AF: 0.288

GnomAD4 genome AF: 0.248 AC: 37759 AN: 152168 Hom.: 5587 Cov.: 32 AF XY: 0.253 AC XY: 18851 AN XY: 74384

Gnomad4 AFR AF: 0.0931

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.256

Alfa AF: 0.282 Hom.: 8316

Bravo AF: 0.236

Asia WGS AF: 0.438 AC: 1522 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	11
DANN	Benign	0.71

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: rs750693; hg19: chr9-37733925;