rs1001413

chr19-38876471-T-Cchr19-38876471-T-G

Variant summary

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

The NM_001195833.2(RINL):c.70A>G(p.Asn24Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 1,535,142 control chromosomes in the GnomAD database, including 122,120 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N24S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.40 (12249 hom., cov: 32)
  • Exomes 𝑓: 0.39 (109871 hom.)
• Consequence: RINL NM_001195833.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171

Genes affected

RINL (HGNC:24795): (Ras and Rab interactor like) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in endocytosis. Predicted to be located in actin cytoskeleton and ruffle. [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 (MetaRNN=2.984308E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RINL	NM_001195833.2	c.70A>G	p.Asn24Asp	missense_variant	3/12	ENST00000591812.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RINL	ENST00000591812.2	c.70A>G	p.Asn24Asp	missense_variant	3/12	2	NM_001195833.2	P2

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60463 AN: 151916 Hom.: 12237 Cov.: 32

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.397

GnomAD3 exomes AF: 0.414 AC: 56680 AN: 136936 Hom.: 12388 AF XY: 0.403 AC XY: 29898 AN XY: 74272

Gnomad AFR exome AF: 0.362

Gnomad AMR exome AF: 0.515

Gnomad ASJ exome AF: 0.422

Gnomad EAS exome AF: 0.607

Gnomad SAS exome AF: 0.286

Gnomad FIN exome AF: 0.439

Gnomad NFE exome AF: 0.388

Gnomad OTH exome AF: 0.402

GnomAD4 exome AF: 0.394 AC: 544927 AN: 1383108 Hom.: 109871 Cov.: 39 AF XY: 0.391 AC XY: 266935 AN XY: 682526

Gnomad4 AFR exome AF: 0.357

Gnomad4 AMR exome AF: 0.513

Gnomad4 ASJ exome AF: 0.427

Gnomad4 EAS exome AF: 0.619

Gnomad4 SAS exome AF: 0.288

Gnomad4 FIN exome AF: 0.448

Gnomad4 NFE exome AF: 0.389

Gnomad4 OTH exome AF: 0.399

GnomAD4 genome AF: 0.398 AC: 60505 AN: 152034 Hom.: 12249 Cov.: 32 AF XY: 0.401 AC XY: 29773 AN XY: 74306

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.610

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.394

Alfa AF: 0.394 Hom.: 20707

Bravo AF: 0.405

TwinsUK AF: 0.386 AC: 1430

ALSPAC AF: 0.390 AC: 1502

ExAC AF: 0.282 AC: 5304

Asia WGS AF: 0.440 AC: 1530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
Cadd	Benign	6.6
Dann	Benign	0.80
DEOGEN2	Benign	0.00079	T
FATHMM_MKL	Benign	0.034	N
MetaRNN	Benign	0.000030	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.35	T
Sift4G	Benign	0.38	T
Vest4		0.014
MPC		0.12
GERP RS		-0.17
Varity_R		0.055
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1001413; hg19: chr19-39367111; COSMIC: COSV50874526; COSMIC: COSV50874526;