rs1001413

Variant names:

• chr19-38876471-T-C
• rs1001413
• NM_001195833.2:c.70A>G

Your query was ambiguous. Multiple possible variants found:

• chr19-38876471-T-C
• chr19-38876471-T-G

Variant summary

Our verdict is Benign. The variant received -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. 11/16 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
• Publications: 34 publications found

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]

ENSG00000269050 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195833.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RINL	NM_001195833.2	MANE Select	c.70A>G	p.Asn24Asp	missense	Exon 3 of 12	NP_001182762.1
	RINL	NM_198445.4		c.-273A>G		5_prime_UTR	Exon 3 of 12	NP_940847.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RINL	ENST00000591812.2	TSL:2 MANE Select	c.70A>G	p.Asn24Asp	missense	Exon 3 of 12	ENSP00000467107.1
	RINL	ENST00000589111.5	TSL:2	n.135A>G		non_coding_transcript_exon	Exon 3 of 9
	RINL	ENST00000598048.1	TSL:4	n.353A>G		non_coding_transcript_exon	Exon 2 of 3

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

GnomAD2 exomes AF: 0.414 AC: 56680 AN: 136936 AF XY: 0.403

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 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

African (AFR) AF: 0.357 AC: 11260 AN: 31572

American (AMR) AF: 0.513 AC: 18303 AN: 35690

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 10744 AN: 25164

East Asian (EAS) AF: 0.619 AC: 22113 AN: 35730

South Asian (SAS) AF: 0.288 AC: 22802 AN: 79218

European-Finnish (FIN) AF: 0.448 AC: 15197 AN: 33928

Middle Eastern (MID) AF: 0.315 AC: 1789 AN: 5680

European-Non Finnish (NFE) AF: 0.389 AC: 419632 AN: 1078238

Other (OTH) AF: 0.399 AC: 23087 AN: 57888

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

African (AFR) AF: 0.362 AC: 15015 AN: 41482

American (AMR) AF: 0.458 AC: 6994 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1427 AN: 3470

East Asian (EAS) AF: 0.610 AC: 3145 AN: 5158

South Asian (SAS) AF: 0.284 AC: 1369 AN: 4816

European-Finnish (FIN) AF: 0.447 AC: 4719 AN: 10562

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26640 AN: 67966

Other (OTH) AF: 0.394 AC: 832 AN: 2110

Alfa AF: 0.395 Hom.: 42397

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 v4.9

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
PhyloP100		0.17
PrimateAI	Benign	0.35	T
Sift4G	Benign	0.38	T
Vest4		0.014
MPC		0.12
GERP RS		-0.17
PromoterAI		-0.016	Neutral
Varity_R		0.055
gMVP		0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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