chr2-73088042-C-A

Variant names:

• chr2-73088042-C-A
• rs201414059
• NM_001371272.1:c.1568+8G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001371272.1(RAB11FIP5):​c.1568+8G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,427,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RAB11FIP5 NM_001371272.1 splice_region, intron
• Scores: Splicing: ADA: 0.00003343
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610
• Publications: 0 publications found

Genes affected

RAB11FIP5 (HGNC:24845): (RAB11 family interacting protein 5) Enables gamma-tubulin binding activity. Involved in cellular response to acidic pH; negative regulation of adiponectin secretion; and regulation of protein localization to cell surface. Located in centriolar satellite and mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB11FIP5	NM_001371272.1	c.1568+8G>T		splice_region_variant, intron_variant	Intron 3 of 5	ENST00000486777.7	NP_001358201.1
RAB11FIP5	NM_015470.3	c.1568+8G>T		splice_region_variant, intron_variant	Intron 3 of 4		NP_056285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB11FIP5	ENST00000486777.7	c.1568+8G>T		splice_region_variant, intron_variant	Intron 3 of 5	5	NM_001371272.1	ENSP00000489752.1
RAB11FIP5	ENST00000258098.6	c.1568+8G>T		splice_region_variant, intron_variant	Intron 3 of 4	1		ENSP00000258098.6
RAB11FIP5	ENST00000479196.1	n.279+8G>T		splice_region_variant, intron_variant	Intron 1 of 1	3
RAB11FIP5	ENST00000493523.2	n.1477+8G>T		splice_region_variant, intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1427176 Hom.: 0 Cov.: 32 AF XY: 0.00000142 AC XY: 1 AN XY: 705676

African (AFR) AF: 0.00 AC: 0 AN: 32666

American (AMR) AF: 0.00 AC: 0 AN: 42034

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23428

East Asian (EAS) AF: 0.00 AC: 0 AN: 39416

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79636

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5592

European-Non Finnish (NFE) AF: 9.14e-7 AC: 1 AN: 1093994

Other (OTH) AF: 0.00 AC: 0 AN: 58856

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.80
DANN	Benign	0.69
PhyloP100		-0.061

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000033
dbscSNV1_RF	Benign	0.0
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

Other links and lift over

dbSNP: rs201414059; hg19: chr2-73315170;