2-218040922-T-C

Position:

• chr2-218040922-T-C

Variant summary

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

The ENST00000457754.6(RUFY4):​c.-1158+5528T>C variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0992 in 151,860 control chromosomes in the GnomAD database, including 2,344 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 0.099 (2344 hom., cov: 30)
• Consequence: RUFY4 ENST00000457754.6 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.16

Genes affected

RUFY4 (HGNC:24804): (RUN and FYVE domain containing 4) Enables phosphatidylinositol-3-phosphate binding activity. Involved in autophagosome assembly; cellular response to interleukin-4; and positive regulation of macroautophagy. Located in autophagosome. [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 = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUFY4	NR_034176.2	n.329+5528T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUFY4	ENST00000457754.6	c.-1158+5528T>C		intron_variant, NMD_transcript_variant		2		ENSP00000410091
RUFY4	ENST00000463618.6	n.194+5528T>C		intron_variant, non_coding_transcript_variant		5
RUFY4	ENST00000465568.5	n.89+5738T>C		intron_variant, non_coding_transcript_variant		5
RUFY4	ENST00000497857.5	n.435+5528T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0990 AC: 15021 AN: 151742 Hom.: 2332 Cov.: 30

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0419

Gnomad ASJ AF: 0.0185

Gnomad EAS AF: 0.00330

Gnomad SAS AF: 0.0465

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00177

Gnomad OTH AF: 0.0794

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

GnomAD4 genome AF: 0.0992 AC: 15067 AN: 151860 Hom.: 2344 Cov.: 30 AF XY: 0.0962 AC XY: 7146 AN XY: 74246

Gnomad4 AFR AF: 0.335

Gnomad4 AMR AF: 0.0418

Gnomad4 ASJ AF: 0.0185

Gnomad4 EAS AF: 0.00331

Gnomad4 SAS AF: 0.0462

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00178

Gnomad4 OTH AF: 0.0781

Alfa AF: 0.0156 Hom.: 513

Bravo AF: 0.112

Asia WGS AF: 0.0450 AC: 157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.038
DANN	Benign	0.33

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10498057; hg19: chr2-218905645;