Genetic Variant FAM204A:c.651-7C>A (chr10-118310915-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_022063.3(FAM204A):c.651-7C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 1,575,166 control chromosomes in the GnomAD database, including 194,812 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.43 ( 15312 hom., cov: 31)

Exomes 𝑓: 0.50 ( 179500 hom. )

Consequence

FAM204A
NM_022063.3 splice_region, intron

Scores

Splicing: ADA: 0.00006456

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.29

Publications

11 publications found

Variant links:

Genes affected

FAM204A (HGNC:25794): (family with sequence similarity 204 member A)

FAM204A 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=-0.82).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
FAM204A	NM_022063.3 link	c.651-7C>A	splice_region_variant, intron_variant	Intron 8 of 8	ENST00000369183.9	NP_071346.1	Q9H8W3
FAM204A	NM_001134672.2 link	c.651-7C>A	splice_region_variant, intron_variant	Intron 7 of 7		NP_001128144.1	Q9H8W3
FAM204A	XM_005270024.2 link	c.672-7C>A	splice_region_variant, intron_variant	Intron 9 of 9		XP_005270081.1
FAM204A	XM_047425619.1 link	c.651-7C>A	splice_region_variant, intron_variant	Intron 9 of 9		XP_047281575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM204A	ENST00000369183.9 link	c.651-7C>A		splice_region_variant, intron_variant	Intron 8 of 8	1	NM_022063.3	ENSP00000358183.4		Q9H8W3

Frequencies

GnomAD3 genomes

AF:

0.433

AC:

65619

AN:

151448

Hom.:

15310

Cov.:

show subpopulations

Gnomad AFR

AF:

0.253

Gnomad AMI

AF:

0.504

Gnomad AMR

AF:

0.521

Gnomad ASJ

AF:

0.583

Gnomad EAS

AF:

0.442

Gnomad SAS

AF:

0.483

Gnomad FIN

AF:

0.423

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.509

Gnomad OTH

AF:

0.488

GnomAD2 exomes

AF:

0.478

AC:

109009

AN:

228222

AF XY:

0.484

show subpopulations

Gnomad AFR exome

AF:

0.245

Gnomad AMR exome

AF:

0.520

Gnomad ASJ exome

AF:

0.582

Gnomad EAS exome

AF:

0.445

Gnomad FIN exome

AF:

0.409

Gnomad NFE exome

AF:

0.508

Gnomad OTH exome

AF:

0.504

GnomAD4 exome

AF:

0.498

AC:

708712

AN:

1423600

Hom.:

179500

Cov.:

AF XY:

0.498

AC XY:

353113

AN XY:

708660

show subpopulations

African (AFR)

AF:

0.239

AC:

7626

AN:

31932

American (AMR)

AF:

0.520

AC:

19703

AN:

37896

Ashkenazi Jewish (ASJ)

AF:

0.580

AC:

14769

AN:

25474

East Asian (EAS)

AF:

0.424

AC:

16604

AN:

39138

South Asian (SAS)

AF:

0.482

AC:

38720

AN:

80386

European-Finnish (FIN)

AF:

0.408

AC:

21454

AN:

52616

Middle Eastern (MID)

AF:

0.562

AC:

3147

AN:

5600

European-Non Finnish (NFE)

AF:

0.511

AC:

557430

AN:

1091602

Other (OTH)

AF:

0.496

AC:

29259

AN:

58956

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

14903

29806

44708

59611

74514

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16004

32008

48012

64016

80020

<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:

0.433

AC:

65641

AN:

151566

Hom.:

15312

Cov.:

AF XY:

0.433

AC XY:

32075

AN XY:

74044

show subpopulations

African (AFR)

AF:

0.253

AC:

10425

AN:

41248

American (AMR)

AF:

0.522

AC:

7953

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.583

AC:

2023

AN:

3468

East Asian (EAS)

AF:

0.442

AC:

2282

AN:

5164

South Asian (SAS)

AF:

0.483

AC:

2320

AN:

4802

European-Finnish (FIN)

AF:

0.423

AC:

4413

AN:

10426

Middle Eastern (MID)

AF:

0.589

AC:

172

AN:

292

European-Non Finnish (NFE)

AF:

0.509

AC:

34568

AN:

67904

Other (OTH)

AF:

0.488

AC:

1026

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1802

3604

5405

7207

9009

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

606

1212

1818

2424

3030

<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:

0.508

Hom.:

27194

Bravo

AF:

0.435

Asia WGS

AF:

0.431

AC:

1500

AN:

3468

EpiCase

AF:

0.531

EpiControl

AF:

0.538

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.0

(source)

DANN

Benign

0.51

PhyloP100

-2.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000065

dbscSNV1_RF

Benign

0.020

SpliceAI score (max)

0.020

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