rs12522164

Variant names:

• chr5-131214920-G-A
• rs12522164
• XM_047417393.1:c.-797+4757G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-131214920-G-A
• chr5-131214920-G-T

Variant summary

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

The XM_047417393.1(CDC42SE2):​c.-797+4757G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0985 in 152,264 control chromosomes in the GnomAD database, including 920 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 0.099 (920 hom., cov: 32)
• Consequence: CDC42SE2 XM_047417393.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.295

Genes affected

CDC42SE2 (HGNC:18547): (CDC42 small effector 2) Enables signaling adaptor activity. Involved in regulation of signal transduction. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

HINT1 (HGNC:4912): (histidine triad nucleotide binding protein 1) This gene encodes a protein that hydrolyzes purine nucleotide phosphoramidates substrates, including AMP-morpholidate, AMP-N-alanine methyl ester, AMP-alpha-acetyl lysine methyl ester, and AMP-NH2. The encoded protein interacts with these substrates via a histidine triad motif. This gene is considered a tumor suppressor gene. In addition, mutations in this gene can cause autosomal recessive neuromyotonia and axonal neuropathy. There are several related pseudogenes on chromosome 7. Several transcript variants have been observed. [provided by RefSeq, Dec 2015]

ENSG00000290020 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC42SE2	XM_047417393.1	c.-797+4757G>A		intron_variant	Intron 1 of 8		XP_047273349.1
CDC42SE2	XM_047417396.1	c.-1028+4757G>A		intron_variant	Intron 1 of 10		XP_047273352.1
LOC124901061	XR_007058931.1	n.524-4767C>T		intron_variant	Intron 1 of 1
LOC124901061	XR_007058932.1	n.112-4767C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HINT1	ENST00000506207.2	n.108+9441C>T		intron_variant	Intron 1 of 3	5
ENSG00000290020	ENST00000702509.1	n.116+4757G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0986 AC: 15001 AN: 152144 Hom.: 918 Cov.: 32

Gnomad AFR AF: 0.0381

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0951

Gnomad ASJ AF: 0.0435

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.0970

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

GnomAD4 genome AF: 0.0985 AC: 15000 AN: 152264 Hom.: 920 Cov.: 32 AF XY: 0.101 AC XY: 7480 AN XY: 74426

Gnomad4 AFR AF: 0.0380

Gnomad4 AMR AF: 0.0948

Gnomad4 ASJ AF: 0.0435

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.0989

Alfa AF: 0.0371 Hom.: 36

Bravo AF: 0.0889

Asia WGS AF: 0.135 AC: 472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.8
DANN	Benign	0.66

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12522164; hg19: chr5-130550613;