chr12-124129992-T-C

Variant names:

• chr12-124129992-T-C
• rs7969148
• NM_001204299.3:c.-233-19603T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001204299.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF664-RFLNA	NM_001204299.3		c.-233-19603T>C		intron	N/A	NP_001191228.1
	ZNF664-RFLNA	NM_001347902.2		c.-233-19603T>C		intron	N/A	NP_001334831.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFLNA	ENST00000389727.8	TSL:5	c.-233-19603T>C		intron	N/A	ENSP00000374377.4
	RFLNA	ENST00000545615.1	TSL:3	n.195-19603T>C		intron	N/A

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

African (AFR) AF: 0.337 AC: 13476 AN: 39960

American (AMR) AF: 0.143 AC: 2112 AN: 14772

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1127 AN: 3454

East Asian (EAS) AF: 0.0210 AC: 107 AN: 5094

South Asian (SAS) AF: 0.247 AC: 1163 AN: 4714

European-Finnish (FIN) AF: 0.104 AC: 1018 AN: 9804

Middle Eastern (MID) AF: 0.293 AC: 82 AN: 280

European-Non Finnish (NFE) AF: 0.211 AC: 14250 AN: 67602

Other (OTH) AF: 0.225 AC: 463 AN: 2058

Alfa AF: 0.219 Hom.: 4999

Bravo AF: 0.235

Asia WGS AF: 0.130 AC: 452 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.41
DANN	Benign	0.58
PhyloP100		-0.45

Splicing

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

Other links and lift over

dbSNP: rs7969148; hg19: chr12-124614538;