chr6-96617336-G-A

Position:

• chr6-96617336-G-A

Variant summary

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

The NM_001322466.2(FHL5):​c.*1564G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,114 control chromosomes in the GnomAD database, including 2,724 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 0.18 (2724 hom., cov: 33)
• Consequence: FHL5 NM_001322466.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.195

Genes affected

FHL5 (HGNC:17371): (four and a half LIM domains 5) The protein encoded by this gene is coordinately expressed with activator of cAMP-responsive element modulator (CREM). It is associated with CREM and confers a powerful transcriptional activation function. CREM acts as a transcription factor essential for the differentiation of spermatids into mature spermatozoa. There are multiple polyadenylation sites found in this gene. Polymorphisms in this gene may be associated with susceptibility for migraine headaches. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FHL5	NM_001322466.2	c.*1564G>A		3_prime_UTR_variant	6/6	ENST00000450218.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FHL5	ENST00000450218.6	c.*1564G>A		3_prime_UTR_variant	6/6	5	NM_001322466.2	P1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27485 AN: 151996 Hom.: 2725 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.0437

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.181 AC: 27474 AN: 152114 Hom.: 2724 Cov.: 33 AF XY: 0.179 AC XY: 13294 AN XY: 74352

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.0438

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.204

Alfa AF: 0.191 Hom.: 365

Bravo AF: 0.177

Asia WGS AF: 0.110 AC: 384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	0.15

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11759769; hg19: chr6-97065212;