6-122781200-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_001446.5(FABP7):c.348+6T>C variant causes a splice donor region, intron change. The variant allele was found at a frequency of 0.00231 in 1,613,816 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (43 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (33 hom.)
• Consequence: FABP7 NM_001446.5 splice_donor_region, intron
• Scores: Splicing: ADA: 0.6862
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.28

Genes affected

FABP7 (HGNC:3562): (fatty acid binding protein 7) The gene encodes a small, highly conserved cytoplasmic protein that bind long-chain fatty acids and other hydrophobic ligands. The encoded protein is important in the establishment of the radial glial fiber in the developing brain. Alternative splicing and promoter usage results in multiple transcript variants encoding different isoforms. Pseudogenes of this gene are found on multiple chromosomes. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 6-122781200-T-C is Benign according to our data. Variant chr6-122781200-T-C is described in ClinVar as [Benign]. Clinvar id is 782479.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0126 (1919/152260) while in subpopulation AFR AF= 0.0414 (1718/41542). AF 95% confidence interval is 0.0397. There are 43 homozygotes in gnomad4. There are 898 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 42 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FABP7	NM_001446.5	c.348+6T>C		splice_donor_region_variant, intron_variant		ENST00000368444.8
FABP7	NM_001319039.2	c.354T>C	p.Ser118=	synonymous_variant	3/3
FABP7	NM_001319041.2	c.*689T>C		3_prime_UTR_variant	2/2
FABP7	NM_001319042.2	c.336+6T>C		splice_donor_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FABP7	ENST00000356535.4	c.354T>C	p.Ser118=	synonymous_variant	3/3	1
FABP7	ENST00000368444.8	c.348+6T>C		splice_donor_region_variant, intron_variant		1	NM_001446.5	P1

Frequencies

GnomAD3 genomes AF: 0.0126 AC: 1919 AN: 152142 Hom.: 42 Cov.: 32

Gnomad AFR AF: 0.0415

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00995

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0129

GnomAD3 exomes AF: 0.00325 AC: 815 AN: 251120 Hom.: 16 AF XY: 0.00240 AC XY: 326 AN XY: 135732

Gnomad AFR exome AF: 0.0413

Gnomad AMR exome AF: 0.00316

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000194

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00123 AC: 1803 AN: 1461556 Hom.: 33 Cov.: 31 AF XY: 0.00106 AC XY: 769 AN XY: 727080

Gnomad4 AFR exome AF: 0.0361

Gnomad4 AMR exome AF: 0.00391

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000189

Gnomad4 OTH exome AF: 0.00333

GnomAD4 genome AF: 0.0126 AC: 1919 AN: 152260 Hom.: 43 Cov.: 32 AF XY: 0.0121 AC XY: 898 AN XY: 74464

Gnomad4 AFR AF: 0.0414

Gnomad4 AMR AF: 0.00994

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00480 Hom.: 9

Bravo AF: 0.0145

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
Cadd	Benign	17
Dann	Benign	0.96

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.69
dbscSNV1_RF	Benign	0.48
SpliceAI score (max)		0.060		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: rs114216518; hg19: chr6-123102345;