12-124288002-A-G

Position:

• chr12-124288002-A-G

Variant summary

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

The NM_001204299.3(ZNF664-RFLNA):​c.-36-23816A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 151,944 control chromosomes in the GnomAD database, including 1,110 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 0.11 (1110 hom., cov: 30)
• Consequence: ZNF664-RFLNA NM_001204299.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.516

Genes affected

ZNF664-RFLNA (HGNC:):

RFLNA (HGNC:27051): (refilin A) Predicted to enable filamin binding activity. Predicted to be involved in several processes, including actin filament bundle organization; negative regulation of bone mineralization involved in bone maturation; and negative regulation of chondrocyte development. Predicted to be located in cytoplasm. Predicted to be active in actin filament bundle. [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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF664-RFLNA	NM_001204299.3	c.-36-23816A>G		intron_variant			NP_001191228.1
ZNF664-RFLNA	NM_001347902.2	c.-36-23816A>G		intron_variant			NP_001334831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RFLNA	ENST00000389727.8	c.-36-23816A>G		intron_variant		5		ENSP00000374377

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16796 AN: 151826 Hom.: 1107 Cov.: 30

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.0882

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0747

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.111 AC: 16821 AN: 151944 Hom.: 1110 Cov.: 30 AF XY: 0.114 AC XY: 8469 AN XY: 74240

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.0882

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.0747

Gnomad4 OTH AF: 0.120

Alfa AF: 0.113 Hom.: 181

Bravo AF: 0.115

Asia WGS AF: 0.203 AC: 702 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.7
DANN	Benign	0.34

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7955740; hg19: chr12-124772548;