Genetic Variant FAM228A:p.His198His (chr2-24190604-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2

The NM_001040710.3(FAM228A):c.594C>T(p.His198His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000609 in 1,588,616 control chromosomes in the GnomAD database, including 4 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 0.0015 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00052 ( 1 hom. )

Consequence

FAM228A
NM_001040710.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.473

Publications

1 publications found

Variant links:

Genes affected

FAM228A (HGNC:34418): (family with sequence similarity 228 member A)

FAM228A links:

ENSG00000276087 (HGNC:):

ENSG00000276087 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP7

Synonymous conserved (PhyloP=-0.473 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040710.3. 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
	FAM228A	NM_001040710.3	MANE Select	c.594C>T	p.His198His	synonymous	Exon 6 of 6	NP_001035800.1	Q86W67

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM228A	ENST00000295150.8	TSL:1 MANE Select	c.594C>T	p.His198His	synonymous	Exon 6 of 6	ENSP00000295150.3	Q86W67
FAM228A	ENST00000965618.1		c.525C>T	p.His175His	synonymous	Exon 5 of 5	ENSP00000635677.1
FAM228A	ENST00000432434.2	TSL:5	c.660+51C>T		intron	N/A	ENSP00000412833.2	H7C3M9

Frequencies

GnomAD3 genomes

AF:

0.00146

AC:

222

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00922

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.00107

AC:

241

AN:

225534

AF XY:

0.000885

show subpopulations

Gnomad AFR exome

AF:

0.00451

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.00954

Gnomad EAS exome

AF:

0.0000595

Gnomad FIN exome

AF:

0.0000490

Gnomad NFE exome

AF:

0.000334

Gnomad OTH exome

AF:

0.00241

GnomAD4 exome

AF:

0.000517

AC:

743

AN:

1436396

Hom.:

Cov.:

AF XY:

0.000515

AC XY:

367

AN XY:

713036

show subpopulations

African (AFR)

AF:

0.00417

AC:

134

AN:

32128

American (AMR)

AF:

0.00154

AC:

AN:

39670

Ashkenazi Jewish (ASJ)

AF:

0.00875

AC:

215

AN:

24560

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39490

South Asian (SAS)

AF:

0.000268

AC:

AN:

82022

European-Finnish (FIN)

AF:

0.0000569

AC:

AN:

52710

Middle Eastern (MID)

AF:

0.00269

AC:

AN:

5202

European-Non Finnish (NFE)

AF:

0.000192

AC:

212

AN:

1101434

Other (OTH)

AF:

0.00137

AC:

AN:

59180

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

115

153

191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00147

AC:

224

AN:

152220

Hom.:

Cov.:

AF XY:

0.00138

AC XY:

103

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.00366

AC:

152

AN:

41550

American (AMR)

AF:

0.00177

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00922

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.000208

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68002

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00129

Hom.:

Bravo

AF:

0.00176

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.96

(source)

DANN

Benign

0.61

PhyloP100

-0.47

Mutation Taster

=100/0

polymorphism

(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