rs1599796

Variant names:

• chr3-119525087-G-A
• rs1599796
• NM_005191.4:c.*701C>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.*701C>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 152,048 control chromosomes in the GnomAD database, including 2,344 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 (2344 hom., cov: 32)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: CD80 NM_005191.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149
• Publications: 23 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD80	NM_005191.4	c.*701C>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000264246.8	NP_005182.1
TIMMDC1	NM_016589.4	c.*1331G>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.*701C>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_005191.4	ENSP00000264246.3
TIMMDC1	ENST00000494664.6	c.*1331G>A		3_prime_UTR_variant	Exon 7 of 7	1	NM_016589.4	ENSP00000418803.1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23441 AN: 151924 Hom.: 2342 Cov.: 32

Gnomad AFR AF: 0.0355

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.168

GnomAD4 exome AF: 0.167 AC: 1 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 1 AN XY: 6

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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: 0.250 AC: 1 AN: 4

Other (OTH) AF: 0.00 AC: 0 AN: 2

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.154 AC: 23448 AN: 152042 Hom.: 2344 Cov.: 32 AF XY: 0.159 AC XY: 11796 AN XY: 74298

African (AFR) AF: 0.0355 AC: 1473 AN: 41516

American (AMR) AF: 0.180 AC: 2751 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 810 AN: 3470

East Asian (EAS) AF: 0.277 AC: 1432 AN: 5172

South Asian (SAS) AF: 0.178 AC: 856 AN: 4820

European-Finnish (FIN) AF: 0.255 AC: 2681 AN: 10532

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

European-Non Finnish (NFE) AF: 0.187 AC: 12725 AN: 67962

Other (OTH) AF: 0.167 AC: 352 AN: 2104

Alfa AF: 0.178 Hom.: 8130

Bravo AF: 0.146

Asia WGS AF: 0.202 AC: 703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.62
PhyloP100		-0.15
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: rs1599796; hg19: chr3-119243934;