rs3746410

chr20-35602948-A-G

Variant summary

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

The XR_007067570.1(LOC124904891):n.1272A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,420 control chromosomes in the GnomAD database, including 5,937 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 0.27 (5928 hom., cov: 30)
  • Exomes 𝑓: 0.18 (9 hom.)
• Consequence: LOC124904891 XR_007067570.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0890

Genes affected

LOC124904891 (HGNC:):

FER1L4 (HGNC:15801): (fer-1 like family member 4 (pseudogene)) Predicted to enable metal ion binding activity. Predicted to be involved in plasma membrane organization. Predicted to be integral component of membrane. [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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124904891	XR_007067570.1	n.1272A>G		non_coding_transcript_exon_variant	1/2
FER1L4	NR_119376.1	n.891+62T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000430275.6	n.891+62T>C		intron_variant, non_coding_transcript_variant		5
FER1L4	ENST00000615531.4	n.823+62T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40596 AN: 151588 Hom.: 5899 Cov.: 30

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.273

GnomAD4 exome AF: 0.183 AC: 131 AN: 714 Hom.: 9 Cov.: 0 AF XY: 0.175 AC XY: 73 AN XY: 418

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.333

Gnomad4 FIN exome AF: 0.180

Gnomad4 NFE exome AF: 0.179

Gnomad4 OTH exome AF: 0.158

GnomAD4 genome AF: 0.268 AC: 40669 AN: 151706 Hom.: 5928 Cov.: 30 AF XY: 0.267 AC XY: 19796 AN XY: 74164

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.281

Alfa AF: 0.254 Hom.: 1055

Bravo AF: 0.270

Asia WGS AF: 0.338 AC: 1175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.2
Dann	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3746410; hg19: chr20-34190870; COSMIC: COSV61513974;