Genetic Variant NM_001763.3:c.-178A>G (chr1-158254492-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001763.3(CD1A):c.-178A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,435,194 control chromosomes in the GnomAD database, including 50,517 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 0.32 ( 8959 hom., cov: 29)

Exomes 𝑓: 0.25 ( 41558 hom. )

Consequence

CD1A
NM_001763.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.881

Publications

20 publications found

Variant links:

Genes affected

CD1A (HGNC:1634): (CD1a molecule) This gene encodes a member of the CD1 family of transmembrane glycoproteins, which are structurally related to the major histocompatibility complex (MHC) proteins and form heterodimers with beta-2-microglobulin. The CD1 proteins mediate the presentation of primarily lipid and glycolipid antigens of self or microbial origin to T cells. The human genome contains five CD1 family genes organized in a cluster on chromosome 1. The CD1 family members are thought to differ in their cellular localization and specificity for particular lipid ligands. The protein encoded by this gene localizes to the plasma membrane and to recycling vesicles of the early endocytic system. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

CD1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CD1A	NM_001763.3 link	c.-178A>G	5_prime_UTR_variant	Exon 1 of 6	ENST00000289429.6	NP_001754.2	P06126
CD1A	NM_001320652.2 link	c.26-592A>G	intron_variant	Intron 1 of 5		NP_001307581.1	P06126
CD1A	XM_024450738.2 link	c.-410-592A>G	intron_variant	Intron 2 of 6		XP_024306506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD1A	ENST00000289429.6 link	c.-178A>G		5_prime_UTR_variant	Exon 1 of 6	1	NM_001763.3	ENSP00000289429.5		P06126

Frequencies

GnomAD3 genomes

AF:

0.321

AC:

48654

AN:

151694

Hom.:

8944

Cov.:

show subpopulations

Gnomad AFR

AF:

0.510

Gnomad AMI

AF:

0.311

Gnomad AMR

AF:

0.286

Gnomad ASJ

AF:

0.241

Gnomad EAS

AF:

0.262

Gnomad SAS

AF:

0.313

Gnomad FIN

AF:

0.257

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.234

Gnomad OTH

AF:

0.307

GnomAD4 exome

AF:

0.249

AC:

318941

AN:

1283382

Hom.:

41558

Cov.:

AF XY:

0.250

AC XY:

156078

AN XY:

624964

show subpopulations

African (AFR)

AF:

0.527

AC:

14957

AN:

28396

American (AMR)

AF:

0.301

AC:

7391

AN:

24544

Ashkenazi Jewish (ASJ)

AF:

0.238

AC:

4552

AN:

19112

East Asian (EAS)

AF:

0.302

AC:

9920

AN:

32798

South Asian (SAS)

AF:

0.310

AC:

20092

AN:

64804

European-Finnish (FIN)

AF:

0.253

AC:

7583

AN:

29992

Middle Eastern (MID)

AF:

0.242

AC:

1011

AN:

4186

European-Non Finnish (NFE)

AF:

0.233

AC:

239356

AN:

1026790

Other (OTH)

AF:

0.267

AC:

14079

AN:

52760

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

13123

26247

39370

52494

65617

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8832

17664

26496

35328

44160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.321

AC:

48711

AN:

151812

Hom.:

8959

Cov.:

AF XY:

0.320

AC XY:

23727

AN XY:

74190

show subpopulations

African (AFR)

AF:

0.509

AC:

21058

AN:

41360

American (AMR)

AF:

0.286

AC:

4363

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.241

AC:

833

AN:

3460

East Asian (EAS)

AF:

0.262

AC:

1342

AN:

5130

South Asian (SAS)

AF:

0.313

AC:

1505

AN:

4804

European-Finnish (FIN)

AF:

0.257

AC:

2718

AN:

10560

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.234

AC:

15878

AN:

67942

Other (OTH)

AF:

0.313

AC:

660

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1558

3116

4675

6233

7791

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

462

924

1386

1848

2310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.263

Hom.:

8570

Bravo

AF:

0.329

Asia WGS

AF:

0.345

AC:

1198

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.1

(source)

DANN

Benign

0.51

PhyloP100

-0.88

PromoterAI

-0.0030

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over