rs463701

Variant names:

• chr16-89532352-A-G
• rs463701
• NM_003119.4:c.1151-111A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-89532352-A-G
• chr16-89532352-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003119.4(SPG7):​c.1151-111A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 1,316,676 control chromosomes in the GnomAD database, including 139,687 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (16660 hom., cov: 33)
  • Exomes 𝑓: 0.45 (123027 hom.)
• Consequence: SPG7 NM_003119.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.383
• Publications: 26 publications found

Genes affected

SPG7 (HGNC:11237): (SPG7 matrix AAA peptidase subunit, paraplegin) This gene encodes a mitochondrial metalloprotease protein that is a member of the AAA family. Members of this protein family share an ATPase domain and have roles in diverse cellular processes including membrane trafficking, intracellular motility, organelle biogenesis, protein folding, and proteolysis. Mutations in this gene cause autosomal recessive spastic paraplegia 7. Two transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Mar 2014]

SPG7 Gene-Disease associations (from GenCC):

• hereditary spastic paraplegia 7

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• lateral sclerosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-89532352-A-G is Benign according to our data. Variant chr16-89532352-A-G is described in ClinVar as Benign. ClinVar VariationId is 1221163.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPG7	NM_003119.4	c.1151-111A>G		intron_variant	Intron 8 of 16	ENST00000645818.2	NP_003110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPG7	ENST00000645818.2	c.1151-111A>G		intron_variant	Intron 8 of 16		NM_003119.4	ENSP00000495795.2

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70553 AN: 151896 Hom.: 16634 Cov.: 33

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.528

GnomAD4 exome AF: 0.453 AC: 527262 AN: 1164662 Hom.: 123027 AF XY: 0.458 AC XY: 271103 AN XY: 591516

African (AFR) AF: 0.438 AC: 11975 AN: 27340

American (AMR) AF: 0.399 AC: 16679 AN: 41768

Ashkenazi Jewish (ASJ) AF: 0.506 AC: 12115 AN: 23960

East Asian (EAS) AF: 0.690 AC: 25955 AN: 37624

South Asian (SAS) AF: 0.558 AC: 43831 AN: 78554

European-Finnish (FIN) AF: 0.450 AC: 21183 AN: 47060

Middle Eastern (MID) AF: 0.580 AC: 2961 AN: 5104

European-Non Finnish (NFE) AF: 0.432 AC: 368233 AN: 852820

Other (OTH) AF: 0.482 AC: 24330 AN: 50432

GnomAD4 genome AF: 0.465 AC: 70621 AN: 152014 Hom.: 16660 Cov.: 33 AF XY: 0.469 AC XY: 34871 AN XY: 74310

African (AFR) AF: 0.434 AC: 17959 AN: 41420

American (AMR) AF: 0.486 AC: 7438 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1721 AN: 3468

East Asian (EAS) AF: 0.672 AC: 3475 AN: 5168

South Asian (SAS) AF: 0.564 AC: 2722 AN: 4824

European-Finnish (FIN) AF: 0.448 AC: 4734 AN: 10572

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30856 AN: 67962

Other (OTH) AF: 0.529 AC: 1117 AN: 2112

Alfa AF: 0.463 Hom.: 27691

Bravo AF: 0.464

Asia WGS AF: 0.611 AC: 2123 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.29
PhyloP100		-0.38
PromoterAI		0.0049	Neutral
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: rs463701; hg19: chr16-89598760;