rs16948098

Variant names:

• chr15-43927409-G-A
• rs16948098
• NM_032892.5:c.103-3100C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-43927409-G-A
• chr15-43927409-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032892.5(FRMD5):​c.103-3100C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0916 in 152,056 control chromosomes in the GnomAD database, including 1,153 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 0.092 (1153 hom., cov: 31)
• Consequence: FRMD5 NM_032892.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.468
• Publications: 16 publications found

Genes affected

FRMD5 (HGNC:28214): (FERM domain containing 5) Enables integrin binding activity and protein kinase binding activity. Involved in negative regulation of cell motility; positive regulation of cell adhesion; and regulation of cell migration. Located in adherens junction. [provided by Alliance of Genome Resources, Apr 2022]

FRMD5 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with eye movement abnormalities and ataxia

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD5	NM_032892.5	c.103-3100C>T		intron_variant	Intron 1 of 13	ENST00000417257.6	NP_116281.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMD5	ENST00000417257.6	c.103-3100C>T		intron_variant	Intron 1 of 13	1	NM_032892.5	ENSP00000403067.1

Frequencies

GnomAD3 genomes AF: 0.0914 AC: 13893 AN: 151938 Hom.: 1143 Cov.: 31

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0525

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0632

Gnomad FIN AF: 0.0142

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.0423

Gnomad OTH AF: 0.0788

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

GnomAD4 genome AF: 0.0916 AC: 13932 AN: 152056 Hom.: 1153 Cov.: 31 AF XY: 0.0882 AC XY: 6551 AN XY: 74310

African (AFR) AF: 0.222 AC: 9185 AN: 41448

American (AMR) AF: 0.0524 AC: 800 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 355 AN: 3464

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5168

South Asian (SAS) AF: 0.0626 AC: 299 AN: 4778

European-Finnish (FIN) AF: 0.0142 AC: 150 AN: 10598

Middle Eastern (MID) AF: 0.0822 AC: 24 AN: 292

European-Non Finnish (NFE) AF: 0.0423 AC: 2876 AN: 68010

Other (OTH) AF: 0.0780 AC: 165 AN: 2116

Alfa AF: 0.0625 Hom.: 1343

Bravo AF: 0.100

Asia WGS AF: 0.0450 AC: 157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.7
DANN	Benign	0.85
PhyloP100		-0.47
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: rs16948098; hg19: chr15-44219607;