rs1599795

Variant names:

• chr3-119525008-T-A
• rs1599795
• NM_005191.4:c.*780A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005191.4(CD80):​c.*780A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,210 control chromosomes in the GnomAD database, including 2,345 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (2345 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: CD80 NM_005191.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.838
• Publications: 24 publications found

Genes affected

CD80 (HGNC:1700): (CD80 molecule) The protein encoded by this gene is a membrane receptor that is activated by the binding of CD28 or CTLA-4. The activated protein induces T-cell proliferation and cytokine production. This protein can act as a receptor for adenovirus subgroup B and may play a role in lupus neuropathy. [provided by RefSeq, Aug 2011]

TIMMDC1 (HGNC:1321): (translocase of inner mitochondrial membrane domain containing 1) Located in mitochondrion and nucleoplasm. Implicated in nuclear type mitochondrial complex I deficiency 31. [provided by Alliance of Genome Resources, Apr 2022]

TIMMDC1 Gene-Disease associations (from GenCC):

• mitochondrial complex I deficiency, nuclear type 31

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Illumina, Labcorp Genetics (formerly Invitae)
• mitochondrial complex I deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Leigh syndrome

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD80	NM_005191.4	c.*780A>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000264246.8	NP_005182.1
TIMMDC1	NM_016589.4	c.*1252T>A		3_prime_UTR_variant	Exon 7 of 7	ENST00000494664.6	NP_057673.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD80	ENST00000264246.8	c.*780A>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_005191.4	ENSP00000264246.3
TIMMDC1	ENST00000494664.6	c.*1252T>A		3_prime_UTR_variant	Exon 7 of 7	1	NM_016589.4	ENSP00000418803.1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23429 AN: 152090 Hom.: 2343 Cov.: 32

Gnomad AFR AF: 0.0354

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.167

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.154 AC: 23436 AN: 152208 Hom.: 2345 Cov.: 32 AF XY: 0.158 AC XY: 11790 AN XY: 74414

African (AFR) AF: 0.0354 AC: 1471 AN: 41570

American (AMR) AF: 0.180 AC: 2750 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 811 AN: 3472

East Asian (EAS) AF: 0.276 AC: 1430 AN: 5178

South Asian (SAS) AF: 0.177 AC: 855 AN: 4822

European-Finnish (FIN) AF: 0.253 AC: 2676 AN: 10576

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12723 AN: 68006

Other (OTH) AF: 0.167 AC: 353 AN: 2114

Alfa AF: 0.158 Hom.: 278

Bravo AF: 0.146

Asia WGS AF: 0.202 AC: 704 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 17, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 24981235) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Benign	0.88
PhyloP100		0.84
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: rs1599795; hg19: chr3-119243855;