rs9517312

Variant names:

• chr13-98451601-G-A
• rs9517312
• NM_005766.4:c.*3284G>A

Variant summary

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

The NM_005766.4(FARP1):​c.*3284G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 151,968 control chromosomes in the GnomAD database, including 3,628 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 0.21 (3628 hom., cov: 32)
  • Exomes 𝑓: 0.083 (0 hom.)
• Consequence: FARP1 NM_005766.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135
• Publications: 3 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FARP1	NM_005766.4	c.*3284G>A		3_prime_UTR_variant	Exon 27 of 27	ENST00000319562.11	NP_005757.1
STK24	NM_001032296.4	c.*1572C>T		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.*3284G>A		3_prime_UTR_variant	Exon 27 of 27	1	NM_005766.4	ENSP00000322926.6
STK24	ENST00000539966.6	c.*1572C>T		3_prime_UTR_variant	Exon 11 of 11	1	NM_001032296.4	ENSP00000442539.2
STK24	ENST00000397517.6	c.*1572C>T		3_prime_UTR_variant	Exon 10 of 10	2		ENSP00000380651.3
STK24	ENST00000376554.8	c.*1572C>T		3_prime_UTR_variant	Exon 5 of 5	5		ENSP00000365737.4

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32609 AN: 151838 Hom.: 3622 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.216

GnomAD4 exome AF: 0.0833 AC: 1 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 8

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.100 AC: 1 AN: 10

Other (OTH) AF: 0.00 AC: 0 AN: 2

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.215 AC: 32636 AN: 151956 Hom.: 3628 Cov.: 32 AF XY: 0.211 AC XY: 15652 AN XY: 74276

African (AFR) AF: 0.242 AC: 10002 AN: 41414

American (AMR) AF: 0.183 AC: 2789 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 813 AN: 3466

East Asian (EAS) AF: 0.143 AC: 737 AN: 5168

South Asian (SAS) AF: 0.212 AC: 1017 AN: 4806

European-Finnish (FIN) AF: 0.168 AC: 1771 AN: 10546

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

European-Non Finnish (NFE) AF: 0.218 AC: 14794 AN: 67968

Other (OTH) AF: 0.219 AC: 461 AN: 2108

Alfa AF: 0.216 Hom.: 1684

Bravo AF: 0.215

Asia WGS AF: 0.191 AC: 662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.6
DANN	Benign	0.56
PhyloP100		-0.14
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: rs9517312; hg19: chr13-99103855;