rs825453

Positions:

• chr12-124024211-A-T

Variant summary

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

The NM_001204299.3(ZNF664-RFLNA):​c.-234+50191A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 151,974 control chromosomes in the GnomAD database, including 22,363 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 0.54 (22363 hom., cov: 33)
• Consequence: ZNF664-RFLNA NM_001204299.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.414

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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF664-RFLNA	NM_001204299.3	c.-234+50191A>T		intron_variant
ZNF664-RFLNA	NM_001347902.2	c.-234+50191A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RFLNA	ENST00000389727.8	c.-234+50191A>T		intron_variant		5
RFLNA	ENST00000545615.1	n.194+50191A>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81725 AN: 151856 Hom.: 22363 Cov.: 33

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.561

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

GnomAD4 genome AF: 0.538 AC: 81744 AN: 151974 Hom.: 22363 Cov.: 33 AF XY: 0.537 AC XY: 39862 AN XY: 74298

Gnomad4 AFR AF: 0.436

Gnomad4 AMR AF: 0.503

Gnomad4 ASJ AF: 0.596

Gnomad4 EAS AF: 0.479

Gnomad4 SAS AF: 0.615

Gnomad4 FIN AF: 0.560

Gnomad4 NFE AF: 0.599

Gnomad4 OTH AF: 0.557

Alfa AF: 0.570 Hom.: 3133

Bravo AF: 0.528

Asia WGS AF: 0.543 AC: 1891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.89
DANN	Benign	0.48

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: rs825453; hg19: chr12-124508758;