rs4878712

Variant names:

• chr9-37654260-G-A
• rs4878712
• NM_014907.3:c.-5+3166G>A

Variant summary

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

The NM_014907.3(FRMPD1):​c.-5+3166G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 152,080 control chromosomes in the GnomAD database, including 21,738 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 0.52 (21738 hom., cov: 32)
• Consequence: FRMPD1 NM_014907.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMPD1	NM_014907.3	c.-5+3166G>A		intron_variant	Intron 1 of 15	ENST00000377765.8	NP_055722.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMPD1	ENST00000377765.8	c.-5+3166G>A		intron_variant	Intron 1 of 15	1	NM_014907.3	ENSP00000366995.3
ENSG00000255872	ENST00000540557.1	n.*1135+38882C>T		intron_variant	Intron 11 of 11	5		ENSP00000457548.1

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78930 AN: 151962 Hom.: 21710 Cov.: 32

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.520 AC: 79015 AN: 152080 Hom.: 21738 Cov.: 32 AF XY: 0.519 AC XY: 38595 AN XY: 74332

Gnomad4 AFR AF: 0.699

Gnomad4 AMR AF: 0.481

Gnomad4 ASJ AF: 0.408

Gnomad4 EAS AF: 0.623

Gnomad4 SAS AF: 0.566

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.517

Alfa AF: 0.453 Hom.: 8801

Bravo AF: 0.529

Asia WGS AF: 0.586 AC: 2037 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.98
DANN	Benign	0.64

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: rs4878712; hg19: chr9-37654257; COSMIC: COSV66702549;