chr5-141515918-A-ATT

Variant names:

• chr5-141515918-A-ATT
• rs550954506
• NM_005219.5:c.*931_*932dupAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_005219.5(DIAPH1):​c.*931_*932dupAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00753 in 151,278 control chromosomes in the GnomAD database, including 18 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0075 (18 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DIAPH1 NM_005219.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

Genes affected

DIAPH1 (HGNC:2876): (diaphanous related formin 1) This gene is a homolog of the Drosophila diaphanous gene, and has been linked to autosomal dominant, fully penetrant, nonsyndromic sensorineural progressive low-frequency hearing loss. Actin polymerization involves proteins known to interact with diaphanous protein in Drosophila and mouse. It has therefore been speculated that this gene may have a role in the regulation of actin polymerization in hair cells of the inner ear. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00753 (1139/151278) while in subpopulation AFR AF= 0.0263 (1081/41142). AF 95% confidence interval is 0.025. There are 18 homozygotes in gnomad4. There are 534 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1139 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIAPH1	NM_005219.5	c.*931_*932dupAA		3_prime_UTR_variant	Exon 28 of 28	ENST00000389054.8	NP_005210.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIAPH1	ENST00000389054	c.*931_*932dupAA		3_prime_UTR_variant	Exon 28 of 28	5	NM_005219.5	ENSP00000373706.4
DIAPH1	ENST00000647433	c.*1050_*1051dupAA		3_prime_UTR_variant	Exon 29 of 29			ENSP00000494675.1
DIAPH1	ENST00000518047.5	c.*931_*932dupAA		downstream_gene_variant		5		ENSP00000428268.2

Frequencies

GnomAD3 genomes AF: 0.00752 AC: 1136 AN: 151162 Hom.: 18 Cov.: 33

Gnomad AFR AF: 0.0263

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00237

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000590

Gnomad OTH AF: 0.00868

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 98 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 48

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00753 AC: 1139 AN: 151278 Hom.: 18 Cov.: 33 AF XY: 0.00722 AC XY: 534 AN XY: 73940

Gnomad4 AFR AF: 0.0263

Gnomad4 AMR AF: 0.00237

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000590

Gnomad4 OTH AF: 0.00859

Bravo AF: 0.00841

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs550954506; hg19: chr5-140895485;