NM_004860.4:c.10C>T

Variant names:

• chr17-7614523-G-A
• rs974541378
• NM_004860.4:c.10C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_004860.4(FXR2):​c.10C>T​(p.Leu4Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,339,486 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: FXR2 NM_004860.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.40
• Publications: 0 publications found

Genes affected

FXR2 (HGNC:4024): (FMR1 autosomal homolog 2) The protein encoded by this gene is a RNA binding protein containing two KH domains and one RCG box, which is similar to FMRP and FXR1. It associates with polyribosomes, predominantly with 60S large ribosomal subunits. This encoded protein may self-associate or interact with FMRP and FXR1. It may have a role in the development of fragile X cognitive disability syndrome. [provided by RefSeq, Jul 2008]

SHBG (HGNC:10839): (sex hormone binding globulin) This gene encodes a steroid binding protein that was first described as a plasma protein secreted by the liver but is now thought to participate in the regulation of steroid responses. The encoded protein transports androgens and estrogens in the blood, binding each steroid molecule as a dimer formed from identical or nearly identical monomers. Polymorphisms in this gene have been associated with polycystic ovary syndrome and type 2 diabetes mellitus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=3.4 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 14 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004860.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FXR2	NM_004860.4	MANE Select	c.10C>T	p.Leu4Leu	synonymous	Exon 1 of 17	NP_004851.2	P51116
	SHBG	NM_001289114.2		c.-62+412G>A		intron	N/A	NP_001276043.1	I3L145

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FXR2	ENST00000250113.12	TSL:1 MANE Select	c.10C>T	p.Leu4Leu	synonymous	Exon 1 of 17	ENSP00000250113.7	P51116
	SHBG	ENST00000575314.5	TSL:1	c.-62+412G>A		intron	N/A	ENSP00000458559.1	I3L145
	SHBG	ENST00000572262.5	TSL:1	c.-62+412G>A		intron	N/A	ENSP00000459999.1	I3L2X4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000105 AC: 14 AN: 1339486 Hom.: 0 Cov.: 30 AF XY: 0.0000106 AC XY: 7 AN XY: 659070

African (AFR) AF: 0.00 AC: 0 AN: 27416

American (AMR) AF: 0.00 AC: 0 AN: 29728

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23768

East Asian (EAS) AF: 0.00 AC: 0 AN: 30466

South Asian (SAS) AF: 0.00 AC: 0 AN: 73506

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5372

European-Non Finnish (NFE) AF: 0.00000948 AC: 10 AN: 1055266

Other (OTH) AF: 0.0000722 AC: 4 AN: 55376

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	14
DANN	Benign	0.96
PhyloP100		3.4
PromoterAI		-0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs974541378; hg19: chr17-7517841;