NM_001018071.4:c.25+3417C>A

Variant names:

• chr10-48271126-G-T
• rs17009540
• NM_001018071.4:c.25+3417C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001018071.4(FRMPD2):​c.25+3417C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0321 in 152,190 control chromosomes in the GnomAD database, including 96 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 0.032 (96 hom., cov: 32)
• Consequence: FRMPD2 NM_001018071.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.606
• Publications: 2 publications found

Genes affected

FRMPD2 (HGNC:28572): (FERM and PDZ domain containing 2) This gene encodes a peripheral membrane protein and is located in a region of chromosome 10q that contains a segmental duplication. This copy of the gene is full-length and is in the telomeric duplicated region. Two other more centromerically proximal copies of the gene are partial and may represent pseudogenes. This full-length gene appears to function in the establishment and maintenance of cell polarization. The protein is recruited to cell-cell junctions in an E-cadherin-dependent manner, and is selectively localized at the basolateral membrane in polarized epithelial cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0321 (4883/152190) while in subpopulation NFE AF = 0.0428 (2908/67982). AF 95% confidence interval is 0.0415. There are 96 homozygotes in GnomAd4. There are 2309 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 96 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMPD2	NM_001018071.4	c.25+3417C>A		intron_variant	Intron 1 of 28	ENST00000374201.8	NP_001018081.4
FRMPD2	XM_047424652.1	c.25+3417C>A		intron_variant	Intron 1 of 21		XP_047280608.1
FRMPD2	XM_011539327.3	c.25+3417C>A		intron_variant	Intron 1 of 15		XP_011537629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMPD2	ENST00000374201.8	c.25+3417C>A		intron_variant	Intron 1 of 28	1	NM_001018071.4	ENSP00000363317.3
FRMPD2	ENST00000636244.1	c.25+3417C>A		intron_variant	Intron 1 of 29	5		ENSP00000490201.1
FRMPD2	ENST00000486151.5	n.132+3417C>A		intron_variant	Intron 1 of 19	2
FRMPD2	ENST00000637395.1	n.25+3417C>A		intron_variant	Intron 1 of 27	5		ENSP00000490362.1

Frequencies

GnomAD3 genomes AF: 0.0321 AC: 4884 AN: 152072 Hom.: 96 Cov.: 32

Gnomad AFR AF: 0.0209

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0208

Gnomad ASJ AF: 0.0326

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0170

Gnomad FIN AF: 0.0472

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0428

Gnomad OTH AF: 0.0287

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

GnomAD4 genome AF: 0.0321 AC: 4883 AN: 152190 Hom.: 96 Cov.: 32 AF XY: 0.0310 AC XY: 2309 AN XY: 74404

African (AFR) AF: 0.0209 AC: 867 AN: 41562

American (AMR) AF: 0.0207 AC: 317 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0326 AC: 113 AN: 3470

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5164

South Asian (SAS) AF: 0.0168 AC: 81 AN: 4808

European-Finnish (FIN) AF: 0.0472 AC: 500 AN: 10598

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0428 AC: 2908 AN: 67982

Other (OTH) AF: 0.0284 AC: 60 AN: 2116

Alfa AF: 0.0169 Hom.: 11

Bravo AF: 0.0285

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.69
DANN	Benign	0.59
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism

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: rs17009540; hg19: chr10-49479169;