Genetic Variant NM_002101.5:c.50-11362G>T (chr2-126678893-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002101.5(GYPC):c.50-11362G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0738 in 152,228 control chromosomes in the GnomAD database, including 436 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 0.074 ( 433 hom., cov: 33)

Exomes 𝑓: 0.18 ( 3 hom. )

Consequence

GYPC
NM_002101.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.25

Publications

2 publications found

Variant links:

Genes affected

GYPC (HGNC:4704): (glycophorin C (Gerbich blood group)) Glycophorin C (GYPC) is an integral membrane glycoprotein. It is a minor species carried by human erythrocytes, but plays an important role in regulating the mechanical stability of red cells. A number of glycophorin C mutations have been described. The Gerbich and Yus phenotypes are due to deletion of exon 3 and 2, respectively. The Webb and Duch antigens, also known as glycophorin D, result from single point mutations of the glycophorin C gene. The glycophorin C protein has very little homology with glycophorins A and B. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]

GYPC Gene-Disease associations (from GenCC):

hereditary elliptocytosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

GYPC 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=-0.96).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0839 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002101.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GYPC	NM_002101.5	MANE Select	c.50-11362G>T	intron	N/A	NP_002092.1
GYPC	NM_016815.4		c.50-14971G>T	intron	N/A	NP_058131.1
GYPC	NM_001256584.2		c.-832-6935G>T	intron	N/A	NP_001243513.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GYPC	ENST00000259254.9	TSL:1 MANE Select	c.50-11362G>T	intron	N/A	ENSP00000259254.4
GYPC	ENST00000409836.3	TSL:1	c.50-14971G>T	intron	N/A	ENSP00000386904.3
GYPC	ENST00000356887.12	TSL:1	c.-832-6935G>T	intron	N/A	ENSP00000349354.7

Frequencies

GnomAD3 genomes

AF:

0.0738

AC:

11212

AN:

152018

Hom.:

434

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0704

Gnomad AMI

AF:

0.0670

Gnomad AMR

AF:

0.0485

Gnomad ASJ

AF:

0.102

Gnomad EAS

AF:

0.00174

Gnomad SAS

AF:

0.0881

Gnomad FIN

AF:

0.0623

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.0857

Gnomad OTH

AF:

0.0862

GnomAD4 exome

AF:

0.185

AC:

AN:

Hom.:

Cov.:

AF XY:

0.152

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.194

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.217

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0737

AC:

11210

AN:

152136

Hom.:

433

Cov.:

AF XY:

0.0727

AC XY:

5410

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.0703

AC:

2920

AN:

41514

American (AMR)

AF:

0.0484

AC:

739

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.102

AC:

355

AN:

3470

East Asian (EAS)

AF:

0.00174

AC:

AN:

5166

South Asian (SAS)

AF:

0.0888

AC:

428

AN:

4818

European-Finnish (FIN)

AF:

0.0623

AC:

660

AN:

10600

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0857

AC:

5827

AN:

67972

Other (OTH)

AF:

0.0848

AC:

179

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

536

1072

1607

2143

2679

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

130

260

390

520

650

<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:

0.0727

Hom.:

287

Bravo

AF:

0.0712

Asia WGS

AF:

0.0590

AC:

204

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.13

(source)

DANN

Benign

0.54

PhyloP100

-1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over