rs750693

Variant names:

• chr9-37733928-T-C
• rs750693
• NM_014907.3:c.1218+103T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

ENSG00000255872 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014907.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMPD1	NM_014907.3	MANE Select	c.1218+103T>C		intron	N/A	NP_055722.2
	FRMPD1	NM_001371223.1		c.1218+103T>C		intron	N/A	NP_001358152.1
	FRMPD1	NM_001371224.1		c.1218+103T>C		intron	N/A	NP_001358153.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMPD1	ENST00000377765.8	TSL:1 MANE Select	c.1218+103T>C		intron	N/A	ENSP00000366995.3
	FRMPD1	ENST00000539465.5	TSL:1	c.1218+103T>C		intron	N/A	ENSP00000444411.1
	ENSG00000255872	ENST00000540557.1	TSL:5	n.*911-5900A>G		intron	N/A	ENSP00000457548.1

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

African (AFR) AF: 0.0970 AC: 1497 AN: 15432

American (AMR) AF: 0.363 AC: 11631 AN: 32014

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 3368 AN: 18018

East Asian (EAS) AF: 0.424 AC: 14992 AN: 35328

South Asian (SAS) AF: 0.450 AC: 27293 AN: 60614

European-Finnish (FIN) AF: 0.337 AC: 14990 AN: 44444

Middle Eastern (MID) AF: 0.193 AC: 446 AN: 2314

European-Non Finnish (NFE) AF: 0.290 AC: 99991 AN: 344332

Other (OTH) AF: 0.288 AC: 8929 AN: 30966

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

African (AFR) AF: 0.0931 AC: 3870 AN: 41546

American (AMR) AF: 0.294 AC: 4498 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 611 AN: 3472

East Asian (EAS) AF: 0.432 AC: 2228 AN: 5162

South Asian (SAS) AF: 0.457 AC: 2204 AN: 4824

European-Finnish (FIN) AF: 0.334 AC: 3533 AN: 10580

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19836 AN: 67982

Other (OTH) AF: 0.256 AC: 540 AN: 2110

Alfa AF: 0.277 Hom.: 10246

Bravo AF: 0.236

Asia WGS AF: 0.438 AC: 1522 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	11
DANN	Benign	0.71
PhyloP100		0.085
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: rs750693; hg19: chr9-37733925;