Variant 17-44904920-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001258400.2(FAM187A):c.1091A>G(p.His364Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 1,550,332 control chromosomes in the GnomAD database, including 57,629 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.26 ( 5290 hom., cov: 32)

Exomes 𝑓: 0.27 ( 52339 hom. )

Consequence

FAM187A
NM_001258400.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.288

Variant links:

Genes affected

FAM187A (HGNC:35153): (family with sequence similarity 187 member A) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

FAM187A links:

GFAP (HGNC:4235): (glial fibrillary acidic protein) This gene encodes one of the major intermediate filament proteins of mature astrocytes. It is used as a marker to distinguish astrocytes from other glial cells during development. Mutations in this gene cause Alexander disease, a rare disorder of astrocytes in the central nervous system. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Oct 2008]

GFAP links:

CCDC103 (HGNC:32700): (coiled-coil domain containing 103) Enables protein homodimerization activity. Involved in axonemal dynein complex assembly; cilium movement; and determination of left/right symmetry. Predicted to be located in axoneme. Predicted to be part of outer dynein arm. Implicated in primary ciliary dyskinesia 17. [provided by Alliance of Genome Resources, Apr 2022]

CCDC103 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.4375658E-4).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FAM187A	NM_001258400.2 linkuse as main transcript	c.1091A>G	p.His364Arg	missense_variant	1/1	ENST00000331733.5
GFAP	NM_002055.5 linkuse as main transcript	c.*2427T>C		3_prime_UTR_variant	9/9	ENST00000588735.3
CCDC103	NM_213607.3 linkuse as main transcript	c.*2103A>G		3_prime_UTR_variant	4/4	ENST00000417826.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM187A	ENST00000331733.5 linkuse as main transcript	c.1091A>G	p.His364Arg	missense_variant	1/1	1	NM_001258400.2	P1
CCDC103	ENST00000417826.3 linkuse as main transcript	c.*2103A>G		3_prime_UTR_variant	4/4	1	NM_213607.3	P1	Q8IW40-1
GFAP	ENST00000588735.3 linkuse as main transcript	c.*2427T>C		3_prime_UTR_variant	9/9	1	NM_002055.5	P1	P14136-1

Frequencies

GnomAD3 genomes

AF:

0.262

AC:

39787

AN:

152000

Hom.:

5285

Cov.:

show subpopulations

Gnomad AFR

AF:

0.233

Gnomad AMI

AF:

0.220

Gnomad AMR

AF:

0.226

Gnomad ASJ

AF:

0.240

Gnomad EAS

AF:

0.251

Gnomad SAS

AF:

0.272

Gnomad FIN

AF:

0.318

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.280

Gnomad OTH

AF:

0.264

GnomAD3 exomes

AF:

0.269

AC:

40187

AN:

149304

Hom.:

5556

AF XY:

0.269

AC XY:

21653

AN XY:

80400

show subpopulations

Gnomad AFR exome

AF:

0.236

Gnomad AMR exome

AF:

0.227

Gnomad ASJ exome

AF:

0.245

Gnomad EAS exome

AF:

0.259

Gnomad SAS exome

AF:

0.287

Gnomad FIN exome

AF:

0.321

Gnomad NFE exome

AF:

0.275

Gnomad OTH exome

AF:

0.263

GnomAD4 exome

AF:

0.273

AC:

382030

AN:

1398214

Hom.:

52339

Cov.:

AF XY:

0.274

AC XY:

188921

AN XY:

689630

show subpopulations

Gnomad4 AFR exome

AF:

0.234

Gnomad4 AMR exome

AF:

0.228

Gnomad4 ASJ exome

AF:

0.238

Gnomad4 EAS exome

AF:

0.215

Gnomad4 SAS exome

AF:

0.284

Gnomad4 FIN exome

AF:

0.316

Gnomad4 NFE exome

AF:

0.277

Gnomad4 OTH exome

AF:

0.263

GnomAD4 genome

AF:

0.262

AC:

39814

AN:

152118

Hom.:

5290

Cov.:

AF XY:

0.261

AC XY:

19430

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.233

Gnomad4 AMR

AF:

0.227

Gnomad4 ASJ

AF:

0.240

Gnomad4 EAS

AF:

0.251

Gnomad4 SAS

AF:

0.271

Gnomad4 FIN

AF:

0.318

Gnomad4 NFE

AF:

0.280

Gnomad4 OTH

AF:

0.262

Alfa

AF:

0.272

Hom.:

5206

Bravo

AF:

0.253

TwinsUK

AF:

0.265

AC:

984

ALSPAC

AF:

0.263

AC:

1015

ExAC

AF:

0.234

AC:

5302

Asia WGS

AF:

0.228

AC:

791

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.0090

DANN

Benign

0.37

DEOGEN2

Benign

0.000016

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0076

LIST_S2

Benign

0.21

MetaRNN

Benign

0.00044

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.66

MutationTaster

Benign

0.000036

PrimateAI

Benign

0.21

PROVEAN

Benign

0.46

REVEL

Benign

0.0080

Sift

Benign

1.0

Sift4G

Benign

0.84

Polyphen

0.0

Vest4

0.0060

ClinPred

0.00069

GERP RS

-8.1

Varity_R

0.028

gMVP

0.45

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over