Genetic Variant CD300LD:c.-11G>A (chr17-74592213-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001115152.2(CD300LD):c.-11G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000797 in 1,609,136 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00082 ( 1 hom. )

Consequence

CD300LD
NM_001115152.2 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.547

Variant links:

Genes affected

CD300LD (HGNC:16848): (CD300 molecule like family member d) Predicted to enable transmembrane signaling receptor activity and virus receptor activity. Predicted to be involved in immune system process. Predicted to act upstream of or within regulation of interleukin-6 production and regulation of tumor necrosis factor production. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CD300LD links:

CD300LD-AS1 (HGNC:26480): (CD300LD antisense RNA 1) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

CD300LD-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CD300LD	NM_001115152.2 link	c.-11G>A	5_prime_UTR_variant	Exon 1 of 4	ENST00000375352.1	NP_001108624.1	Q6UXZ3
CD300LD-AS1	NR_171003.1 link	n.693C>T	non_coding_transcript_exon_variant	Exon 3 of 3
CD300LD-AS1	NR_171004.1 link	n.529C>T	non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CD300LD	ENST00000375352.1 link	c.-11G>A	5_prime_UTR_variant	Exon 1 of 4	1	NM_001115152.2	ENSP00000364501.1	Q6UXZ3
CD300LD-AS1	ENST00000328023.2 link	n.474C>T	non_coding_transcript_exon_variant	Exon 2 of 2	5
CD300LD-AS1	ENST00000392620.5 link	n.529C>T	non_coding_transcript_exon_variant	Exon 3 of 3	2
CD300LD-AS1	ENST00000524389.5 link	n.*52C>T	downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000591

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00113

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000474

AC:

119

AN:

251228

Hom.:

AF XY:

0.000442

AC XY:

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000784

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000818

AC:

1192

AN:

1456820

Hom.:

Cov.:

AF XY:

0.000793

AC XY:

575

AN XY:

724852

show subpopulations

Gnomad4 AFR exome

AF:

0.0000899

Gnomad4 AMR exome

AF:

0.000336

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000267

Gnomad4 FIN exome

AF:

0.000244

Gnomad4 NFE exome

AF:

0.000999

Gnomad4 OTH exome

AF:

0.000465

GnomAD4 genome

AF:

0.000591

AC:

AN:

152316

Hom.:

Cov.:

AF XY:

0.000497

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000216

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00113

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000904

Hom.:

Bravo

AF:

0.000593

EpiCase

AF:

0.000600

EpiControl

AF:

0.000830

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.167C>T (p.S56F) alteration is located in exon 3 (coding exon 1) of the C17orf77 gene. This alteration results from a C to T substitution at nucleotide position 167, causing the serine (S) at amino acid position 56 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.72

DANN

Benign

0.67

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over