12-124129992-T-C

Position:

• chr12-124129992-T-C

Variant summary

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

The NM_001204299.3(ZNF664-RFLNA):​c.-233-19603T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 148,640 control chromosomes in the GnomAD database, including 4,516 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 0.23 (4516 hom., cov: 27)
• Consequence: ZNF664-RFLNA NM_001204299.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.452

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF664-RFLNA	NM_001204299.3	c.-233-19603T>C		intron_variant			NP_001191228.1
ZNF664-RFLNA	NM_001347902.2	c.-233-19603T>C		intron_variant			NP_001334831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RFLNA	ENST00000389727.8	c.-233-19603T>C		intron_variant		5		ENSP00000374377
RFLNA	ENST00000545615.1	n.195-19603T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34016 AN: 148546 Hom.: 4512 Cov.: 27

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.0210

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.286

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.229 AC: 34041 AN: 148640 Hom.: 4516 Cov.: 27 AF XY: 0.222 AC XY: 16095 AN XY: 72376

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.326

Gnomad4 EAS AF: 0.0210

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.225

Alfa AF: 0.216 Hom.: 3719

Bravo AF: 0.235

Asia WGS AF: 0.130 AC: 452 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.41
DANN	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7969148; hg19: chr12-124614538;