rs3852700

Positions:

• chr16-67237955-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000258201.9(FHOD1):​c.642+79A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,495,948 control chromosomes in the GnomAD database, including 20,899 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 0.24 (8942 hom., cov: 33)
  • Exomes 𝑓: 0.093 (11957 hom.)
• Consequence: FHOD1 ENST00000258201.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.262

Genes affected

FHOD1 (HGNC:17905): (formin homology 2 domain containing 1) This gene encodes a protein which is a member of the formin/diaphanous family of proteins. The gene is ubiquitously expressed but is found in abundance in the spleen. The encoded protein has sequence homology to diaphanous and formin proteins within the Formin Homology (FH)1 and FH2 domains. It also contains a coiled-coil domain, a collagen-like domain, two nuclear localization signals, and several potential PKC and PKA phosphorylation sites. It is a predominantly cytoplasmic protein and is expressed in a variety of human cell lines. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

SLC9A5 (HGNC:11078): (solute carrier family 9 member A5) Predicted to enable potassium:proton antiporter activity and sodium:proton antiporter activity. Predicted to be involved in potassium ion transmembrane transport; regulation of intracellular pH; and sodium ion import across plasma membrane. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. Implicated in end stage renal disease. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FHOD1	NM_013241.3	c.642+79A>G		intron_variant		ENST00000258201.9	NP_037373.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FHOD1	ENST00000258201.9	c.642+79A>G		intron_variant		1	NM_013241.3	ENSP00000258201	P1
SLC9A5	ENST00000564704.5	n.273T>C		non_coding_transcript_exon_variant	1/16	1
FHOD1	ENST00000561922.1	c.*155+79A>G		intron_variant, NMD_transcript_variant		2		ENSP00000458085
FHOD1	ENST00000567752.5	n.1223+79A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35750 AN: 152066 Hom.: 8906 Cov.: 33

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0343

Gnomad EAS AF: 0.0210

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0711

Gnomad OTH AF: 0.174

GnomAD4 exome AF: 0.0931 AC: 125158 AN: 1343764 Hom.: 11957 Cov.: 21 AF XY: 0.0933 AC XY: 62682 AN XY: 671554

Gnomad4 AFR exome AF: 0.656

Gnomad4 AMR exome AF: 0.0956

Gnomad4 ASJ exome AF: 0.0394

Gnomad4 EAS exome AF: 0.0187

Gnomad4 SAS exome AF: 0.170

Gnomad4 FIN exome AF: 0.112

Gnomad4 NFE exome AF: 0.0718

Gnomad4 OTH exome AF: 0.110

GnomAD4 genome AF: 0.236 AC: 35846 AN: 152184 Hom.: 8942 Cov.: 33 AF XY: 0.233 AC XY: 17356 AN XY: 74410

Gnomad4 AFR AF: 0.634

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.0343

Gnomad4 EAS AF: 0.0211

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.0711

Gnomad4 OTH AF: 0.173

Alfa AF: 0.117 Hom.: 1152

Bravo AF: 0.250

Asia WGS AF: 0.148 AC: 518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	12
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs3852700; hg19: chr16-67271858;