Genetic Variant NM_138389.4:c.1161+143A>C (chr4-38929476-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_138389.4(FAM114A1):c.1161+143A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 641,218 control chromosomes in the GnomAD database, including 23,519 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 0.24 ( 5044 hom., cov: 33)

Exomes 𝑓: 0.25 ( 18475 hom. )

Consequence

FAM114A1
NM_138389.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.69

Variant links:

Genes affected

FAM114A1 (HGNC:25087): (family with sequence similarity 114 member A1) The protein encoded by this gene belongs to the FAM114 family and may play a role in neuronal cell development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2017]

FAM114A1 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 (BayesDel_noAF=-0.98).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM114A1	NM_138389.4 link	c.1161+143A>C		intron_variant	Intron 10 of 14	ENST00000358869.5	NP_612398.2	Q8IWE2-1A1MMZ0

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FAM114A1	ENST00000358869.5 link	c.1161+143A>C	intron_variant	Intron 10 of 14	1	NM_138389.4	ENSP00000351740.2	Q8IWE2-1
FAM114A1	ENST00000508737.1 link	n.235+143A>C	intron_variant	Intron 1 of 5	1
FAM114A1	ENST00000515037.5 link	c.540+143A>C	intron_variant	Intron 8 of 12	2		ENSP00000424115.1	Q8IWE2-2
FAM114A1	ENST00000512889.1 link	n.*193A>C	downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.245

AC:

37274

AN:

152092

Hom.:

5036

Cov.:

show subpopulations

Gnomad AFR

AF:

0.249

Gnomad AMI

AF:

0.254

Gnomad AMR

AF:

0.306

Gnomad ASJ

AF:

0.348

Gnomad EAS

AF:

0.551

Gnomad SAS

AF:

0.426

Gnomad FIN

AF:

0.0992

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.210

Gnomad OTH

AF:

0.254

GnomAD4 exome

AF:

0.249

AC:

121597

AN:

489008

Hom.:

18475

AF XY:

0.257

AC XY:

66133

AN XY:

257760

show subpopulations

Gnomad4 AFR exome

AF:

0.236

Gnomad4 AMR exome

AF:

0.298

Gnomad4 ASJ exome

AF:

0.332

Gnomad4 EAS exome

AF:

0.552

Gnomad4 SAS exome

AF:

0.413

Gnomad4 FIN exome

AF:

0.110

Gnomad4 NFE exome

AF:

0.200

Gnomad4 OTH exome

AF:

0.260

GnomAD4 genome

AF:

0.245

AC:

37283

AN:

152210

Hom.:

5044

Cov.:

AF XY:

0.246

AC XY:

18287

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.249

Gnomad4 AMR

AF:

0.305

Gnomad4 ASJ

AF:

0.348

Gnomad4 EAS

AF:

0.550

Gnomad4 SAS

AF:

0.426

Gnomad4 FIN

AF:

0.0992

Gnomad4 NFE

AF:

0.210

Gnomad4 OTH

AF:

0.252

Alfa

AF:

0.235

Hom.:

9297

Bravo

AF:

0.259

Asia WGS

AF:

0.451

AC:

1571

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.064

DANN

Benign

0.33

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

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