rs11971020

Variant names:

• chr7-38743344-A-G
• rs11971020
• NM_014396.4:c.2122+58T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-38743344-A-G
• chr7-38743344-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014396.4(VPS41):​c.2122+58T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,597,312 control chromosomes in the GnomAD database, including 36,694 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4884 hom., cov: 33)
  • Exomes 𝑓: 0.19 (31810 hom.)
• Consequence: VPS41 NM_014396.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.340
• Publications: 2 publications found

Genes affected

VPS41 (HGNC:12713): (VPS41 subunit of HOPS complex) Vesicle mediated protein sorting plays an important role in segregation of intracellular molecules into distinct organelles. Genetic studies in yeast have identified more than 40 vacuolar protein sorting (VPS) genes involved in vesicle transport to vacuoles. This gene encodes the human ortholog of yeast Vps41 protein which is also conserved in Drosophila, tomato, and Arabidopsis. Expression studies in yeast and human indicate that this protein may be involved in the formation and fusion of transport vesicles from the Golgi. Several transcript variants encoding different isoforms have been described for this gene, however, the full-length nature of not all is known. [provided by RefSeq, Jul 2008]

VPS41 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia, autosomal recessive 29

  Inheritance: Unknown, AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal recessive cerebellar ataxia-saccadic intrusion syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-38743344-A-G is Benign according to our data. Variant chr7-38743344-A-G is described in ClinVar as Benign. ClinVar VariationId is 1239332.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS41	NM_014396.4	c.2122+58T>C		intron_variant	Intron 24 of 28	ENST00000310301.9	NP_055211.2
VPS41	NM_080631.4	c.2047+58T>C		intron_variant	Intron 23 of 27		NP_542198.2
VPS41	XM_017011988.2	c.967+58T>C		intron_variant	Intron 11 of 15		XP_016867477.1
VPS41	XR_007060008.1	n.2139+58T>C		intron_variant	Intron 24 of 28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS41	ENST00000310301.9	c.2122+58T>C		intron_variant	Intron 24 of 28	1	NM_014396.4	ENSP00000309457.4

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35752 AN: 151996 Hom.: 4876 Cov.: 33

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.194 AC: 279729 AN: 1445198 Hom.: 31810 AF XY: 0.200 AC XY: 143800 AN XY: 719708

African (AFR) AF: 0.353 AC: 11599 AN: 32902

American (AMR) AF: 0.0995 AC: 4401 AN: 44238

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 6116 AN: 25860

East Asian (EAS) AF: 0.421 AC: 16639 AN: 39486

South Asian (SAS) AF: 0.396 AC: 33867 AN: 85518

European-Finnish (FIN) AF: 0.209 AC: 11017 AN: 52824

Middle Eastern (MID) AF: 0.214 AC: 1224 AN: 5724

European-Non Finnish (NFE) AF: 0.165 AC: 181659 AN: 1098926

Other (OTH) AF: 0.221 AC: 13207 AN: 59720

GnomAD4 genome AF: 0.235 AC: 35789 AN: 152114 Hom.: 4884 Cov.: 33 AF XY: 0.239 AC XY: 17796 AN XY: 74342

African (AFR) AF: 0.341 AC: 14142 AN: 41508

American (AMR) AF: 0.134 AC: 2052 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 839 AN: 3472

East Asian (EAS) AF: 0.431 AC: 2225 AN: 5160

South Asian (SAS) AF: 0.419 AC: 2020 AN: 4820

European-Finnish (FIN) AF: 0.210 AC: 2223 AN: 10578

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11540 AN: 67986

Other (OTH) AF: 0.217 AC: 459 AN: 2114

Alfa AF: 0.187 Hom.: 1064

Bravo AF: 0.233

Asia WGS AF: 0.391 AC: 1359 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 16, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.8
DANN	Benign	0.65
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs11971020; hg19: chr7-38782944; COSMIC: COSV59645863;