4-38876573-T-C

Variant names:

• chr4-38876573-T-C
• rs721653
• NM_138389.4:c.-8-1498T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138389.4(FAM114A1):​c.-8-1498T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 152,124 control chromosomes in the GnomAD database, including 18,472 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 0.49 (18472 hom., cov: 33)
• Consequence: FAM114A1 NM_138389.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.671

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM114A1	NM_138389.4	c.-8-1498T>C		intron_variant	Intron 2 of 14	ENST00000358869.5	NP_612398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM114A1	ENST00000358869.5	c.-8-1498T>C		intron_variant	Intron 2 of 14	1	NM_138389.4	ENSP00000351740.2
FAM114A1	ENST00000515037.5	c.-274+8739T>C		intron_variant	Intron 1 of 12	2		ENSP00000424115.1
FAM114A1	ENST00000510213.5	c.-8-1498T>C		intron_variant	Intron 1 of 2	2		ENSP00000422965.1

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74617 AN: 152006 Hom.: 18443 Cov.: 33

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.514

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.491 AC: 74702 AN: 152124 Hom.: 18472 Cov.: 33 AF XY: 0.485 AC XY: 36038 AN XY: 74368

Gnomad4 AFR AF: 0.504

Gnomad4 AMR AF: 0.432

Gnomad4 ASJ AF: 0.574

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.401

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.516

Alfa AF: 0.506 Hom.: 40708

Bravo AF: 0.491

Asia WGS AF: 0.417 AC: 1450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.3
DANN	Benign	0.64

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

Other links and lift over

dbSNP: rs721653; hg19: chr4-38878194;