4-38876573-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138389.4. 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
	FAM114A1	NM_138389.4	MANE Select	c.-8-1498T>C		intron	N/A	NP_612398.2	Q8IWE2-1
	FAM114A1	NM_001375792.1		c.-8-1498T>C		intron	N/A	NP_001362721.1	Q8IWE2-1
	FAM114A1	NM_001350632.2		c.-8-1498T>C		intron	N/A	NP_001337561.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM114A1	ENST00000358869.5	TSL:1 MANE Select	c.-8-1498T>C		intron	N/A	ENSP00000351740.2	Q8IWE2-1
	FAM114A1	ENST00000903774.1		c.-8-1498T>C		intron	N/A	ENSP00000573833.1
	FAM114A1	ENST00000967134.1		c.-8-1498T>C		intron	N/A	ENSP00000637193.1

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

African (AFR) AF: 0.504 AC: 20912 AN: 41466

American (AMR) AF: 0.432 AC: 6605 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 1994 AN: 3472

East Asian (EAS) AF: 0.436 AC: 2262 AN: 5186

South Asian (SAS) AF: 0.401 AC: 1939 AN: 4830

European-Finnish (FIN) AF: 0.482 AC: 5086 AN: 10556

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34209 AN: 68000

Other (OTH) AF: 0.516 AC: 1092 AN: 2116

Alfa AF: 0.504 Hom.: 82527

Bravo AF: 0.491

Asia WGS AF: 0.417 AC: 1450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.3
DANN	Benign	0.64
PhyloP100		-0.67
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

dbSNP: rs721653; hg19: chr4-38878194;