chr2-73088042-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001371272.1(RAB11FIP5):​c.1568+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000576 in 1,579,368 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (9 hom., cov: 33)
  • Exomes 𝑓: 0.00030 (2 hom.)
• Consequence: RAB11FIP5 NM_001371272.1 splice_region, intron
• Scores: Splicing: ADA: 0.00006553
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-73088042-C-T is Benign according to our data. Variant chr2-73088042-C-T is described in ClinVar as [Benign]. Clinvar id is 731080.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB11FIP5	NM_001371272.1	c.1568+8G>A		splice_region_variant, intron_variant	Intron 3 of 5	ENST00000486777.7	NP_001358201.1
RAB11FIP5	NM_015470.3	c.1568+8G>A		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>A		splice_region_variant, intron_variant	Intron 3 of 5	5	NM_001371272.1	ENSP00000489752.1
RAB11FIP5	ENST00000258098.6	c.1568+8G>A		splice_region_variant, intron_variant	Intron 3 of 4	1		ENSP00000258098.6
RAB11FIP5	ENST00000479196.1	n.279+8G>A		splice_region_variant, intron_variant	Intron 1 of 1	3
RAB11FIP5	ENST00000493523.2	n.1477+8G>A		splice_region_variant, intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes AF: 0.00314 AC: 477 AN: 152074 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.0107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.000948 AC: 213 AN: 224714 AF XY: 0.000774

Gnomad AFR exome AF: 0.0110

Gnomad AMR exome AF: 0.000652

Gnomad ASJ exome AF: 0.000138

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000684

Gnomad OTH exome AF: 0.000744

GnomAD4 exome AF: 0.000305 AC: 435 AN: 1427176 Hom.: 2 Cov.: 32 AF XY: 0.000298 AC XY: 210 AN XY: 705676

African (AFR) AF: 0.00998 AC: 326 AN: 32666

American (AMR) AF: 0.000761 AC: 32 AN: 42034

Ashkenazi Jewish (ASJ) AF: 0.0000854 AC: 2 AN: 23428

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39416

South Asian (SAS) AF: 0.000151 AC: 12 AN: 79636

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

Middle Eastern (MID) AF: 0.000179 AC: 1 AN: 5592

European-Non Finnish (NFE) AF: 0.0000192 AC: 21 AN: 1093994

Other (OTH) AF: 0.000680 AC: 40 AN: 58856

GnomAD4 genome AF: 0.00312 AC: 475 AN: 152192 Hom.: 9 Cov.: 33 AF XY: 0.00298 AC XY: 222 AN XY: 74408

African (AFR) AF: 0.0107 AC: 443 AN: 41518

American (AMR) AF: 0.00124 AC: 19 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68002

Other (OTH) AF: 0.00379 AC: 8 AN: 2110

Alfa AF: 0.00255 Hom.: 1

Bravo AF: 0.00368

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.9
DANN	Benign	0.66
PhyloP100		-0.061
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000066
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;