rs7910196

Variant names:

• chr10-13768059-G-A
• rs7910196
• NM_018027.5:c.385-5379C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-13768059-G-A
• chr10-13768059-G-T

Variant summary

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

The NM_018027.5(FRMD4A):​c.385-5379C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.885 in 152,012 control chromosomes in the GnomAD database, including 59,680 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 0.89 (59680 hom., cov: 30)
• Consequence: FRMD4A NM_018027.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• Publications: 6 publications found

Genes affected

FRMD4A (HGNC:25491): (FERM domain containing 4A) This gene encodes a FERM domain-containing protein that regulates epithelial cell polarity. It connects ADP ribosylation factor 6 (ARF6) with the Par protein complex, which regulates the remodeling of adherens junctions and linear actin cable formation during epithelial cell polarization. Polymorphisms in this gene are associated with Alzheimer's disease, and also with nicotine dependence. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

FRMD4A Gene-Disease associations (from GenCC):

• severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018027.5. 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
	FRMD4A	NM_018027.5	MANE Select	c.385-5379C>T		intron	N/A	NP_060497.3
	FRMD4A	NM_001318337.2		c.484-5379C>T		intron	N/A	NP_001305266.1
	FRMD4A	NM_001318336.2		c.433-5379C>T		intron	N/A	NP_001305265.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD4A	ENST00000357447.7	TSL:1 MANE Select	c.385-5379C>T		intron	N/A	ENSP00000350032.2
	FRMD4A	ENST00000495956.3	TSL:2	c.385-5379C>T		intron	N/A	ENSP00000488764.2
	FRMD4A	ENST00000264546.10	TSL:2	c.484-5379C>T		intron	N/A	ENSP00000264546.6

Frequencies

GnomAD3 genomes AF: 0.885 AC: 134453 AN: 151894 Hom.: 59622 Cov.: 30

Gnomad AFR AF: 0.924

Gnomad AMI AF: 0.866

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.830

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.881

Gnomad FIN AF: 0.899

Gnomad MID AF: 0.814

Gnomad NFE AF: 0.855

Gnomad OTH AF: 0.874

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

GnomAD4 genome AF: 0.885 AC: 134571 AN: 152012 Hom.: 59680 Cov.: 30 AF XY: 0.886 AC XY: 65844 AN XY: 74288

African (AFR) AF: 0.924 AC: 38306 AN: 41450

American (AMR) AF: 0.884 AC: 13507 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.830 AC: 2881 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5154 AN: 5164

South Asian (SAS) AF: 0.882 AC: 4239 AN: 4806

European-Finnish (FIN) AF: 0.899 AC: 9482 AN: 10548

Middle Eastern (MID) AF: 0.814 AC: 236 AN: 290

European-Non Finnish (NFE) AF: 0.855 AC: 58130 AN: 67980

Other (OTH) AF: 0.875 AC: 1846 AN: 2110

Alfa AF: 0.865 Hom.: 114495

Bravo AF: 0.888

Asia WGS AF: 0.938 AC: 3262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.90
DANN	Benign	0.50
PhyloP100		0.011
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: rs7910196; hg19: chr10-13810059;