rs7983438

Variant names:

• chr13-98451063-T-C
• rs7983438
• NM_005766.4:c.*2746T>C

Variant summary

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

The NM_005766.4(FARP1):​c.*2746T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,096 control chromosomes in the GnomAD database, including 5,316 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 0.26 (5316 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: FARP1 NM_005766.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 5 publications found

Genes affected

FARP1 (HGNC:3591): (FERM, ARH/RhoGEF and pleckstrin domain protein 1) This gene encodes a protein containing a FERM (4.2, exrin, radixin, moesin) domain, a Dbl homology domain, and two pleckstrin homology domains. These domains are found in guanine nucleotide exchange factors and proteins that link the cytoskeleton to the cell membrane. The encoded protein functions in neurons to promote dendritic growth. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]

STK24 (HGNC:11403): (serine/threonine kinase 24) This gene encodes a serine/threonine protein kinase that functions upstream of mitogen-activated protein kinase (MAPK) signaling. The encoded protein is cleaved into two chains by caspases; the N-terminal fragment (MST3/N) translocates to the nucleus and promotes programmed cells death. There is a pseudogene for this gene on chromosome X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FARP1	NM_005766.4	c.*2746T>C		3_prime_UTR_variant	Exon 27 of 27	ENST00000319562.11	NP_005757.1
STK24	NM_001032296.4	c.*2110A>G		3_prime_UTR_variant	Exon 11 of 11	ENST00000539966.6	NP_001027467.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FARP1	ENST00000319562.11	c.*2746T>C		3_prime_UTR_variant	Exon 27 of 27	1	NM_005766.4	ENSP00000322926.6
STK24	ENST00000539966.6	c.*2110A>G		3_prime_UTR_variant	Exon 11 of 11	1	NM_001032296.4	ENSP00000442539.2
STK24	ENST00000397517.6	c.*2110A>G		3_prime_UTR_variant	Exon 10 of 10	2		ENSP00000380651.3
STK24	ENST00000376554.8	c.*2110A>G		3_prime_UTR_variant	Exon 5 of 5	5		ENSP00000365737.4

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39573 AN: 151970 Hom.: 5306 Cov.: 32

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.261

GnomAD4 exome AF: 0.250 AC: 2 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 2 AN XY: 8

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.167 AC: 1 AN: 6

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.260 AC: 39606 AN: 152088 Hom.: 5316 Cov.: 32 AF XY: 0.255 AC XY: 18957 AN XY: 74374

African (AFR) AF: 0.225 AC: 9319 AN: 41478

American (AMR) AF: 0.246 AC: 3763 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 891 AN: 3470

East Asian (EAS) AF: 0.154 AC: 799 AN: 5176

South Asian (SAS) AF: 0.212 AC: 1019 AN: 4810

European-Finnish (FIN) AF: 0.226 AC: 2391 AN: 10582

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20515 AN: 67982

Other (OTH) AF: 0.260 AC: 549 AN: 2112

Alfa AF: 0.282 Hom.: 3738

Bravo AF: 0.259

Asia WGS AF: 0.194 AC: 675 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.24
DANN	Benign	0.23
PhyloP100		-1.4
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: rs7983438; hg19: chr13-99103317;