dbSNP rs4751651: 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. Variant has been reported in ClinVar as (no stars).

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022063.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM204A	NM_022063.3	MANE Select	c.651-7C>A		splice_region intron	N/A	NP_071346.1	Q9H8W3
	FAM204A	NM_001134672.2		c.651-7C>A		splice_region intron	N/A	NP_001128144.1	Q9H8W3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FAM204A	ENST00000369183.9	TSL:1 MANE Select	c.651-7C>A	splice_region intron	N/A	ENSP00000358183.4	Q9H8W3
FAM204A	ENST00000369172.8	TSL:3	c.651-7C>A	splice_region intron	N/A	ENSP00000358170.4	Q9H8W3
FAM204A	ENST00000885074.1		c.651-7C>A	splice_region intron	N/A	ENSP00000555133.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over